SNPMiner Trials by Shray Alag


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Report for Mutation A118G

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 28 clinical trials

Clinical Trials


1 The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain

Patients undergoing surgery (thyroidectomy and hysterectomy) will postoperatively receive oxycodone intravenously (IV) as pain management with morphine as an escape medicine, if there is insufficient pain relief with oxycodone. Patients' pain and side effects will be registered and after 24 hours they will answer a questionnaire. All included patients will be genotyped accordingly to CYP2D6 and relevant single nucleotide polymorphisms (SNPs), and measures of plasma levels of oxycodone will be performed.

NCT00260260 Postoperative Pain Drug: Oxycodone
MeSH: Pain, Postoperative

Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. --- A118G ---

Primary Outcomes

Measure: Responder (satisfaction with pain treatment in questionnaire and no escape medication)

Measure: Non-responder (dissatisfaction with pain management in questionnaire and/or escape medication)

Measure: Responder status compared to CYP2D6 genotype

Secondary Outcomes

Measure: Registration of pain, side effects and total amount of oxycodone given compared to CYP2D6 genotype and SNPs

2 Pharmacogenetic Investigation of Naltrexone

Despite preclinical evidence supporting the role of the endogenous opioid system in the reinforcing effects of nicotine, the efficacy of the opioid antagonist naltrexone (NTX) as a tobacco dependence treatment remains unresolved. Research is needed to identify those smokers for whom NTX will have the strongest beneficial effects on smoking behavior. The research bridges existing knowledge of genetic, pharmacologic, and behavioral responses to nicotine, and translates this knowledge to treatment for tobacco dependence. The immediate goal was to test whether genetic variation in the mu-opioid receptor gene predicts the effects of naltrexone (NTX) on nicotine reinforcement.

NCT00270231 Tobacco Dependence Drug: Naltrexone Drug: Placebo
MeSH: Tobacco Use Disorder

A key question was whether smokers differ in their responses based on the mu opioid receptor gene (OPRM1) Asn40Asp (A118G) variant. --- Asn40Asp --- --- A118G ---

Primary Outcomes

Description: On day 4 of each study medication period, participants completed a cigarette choice procedure where the subject is asked to take 4 puffs from a nicotinized (nicotine-containing) or a denicotinized (no nicotine) cigarette every 30 minutes for 2 hours (maximum of 24 puffs). The outcome variable is the number of nicotine cigarette choices or puffs out of 24 total puffs during these cigarette choice procedures. Subjects who had the A/A genotype took an average of 18.5 puffs from the nicotine-containing cigarettes. Subjects with the A/G or G/G genotypes took an average of 16.2 puffs from the nicotine-containing cigarettes.

Measure: Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.

Time: 2 hours

3 The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models

Thirty-two healthy volunteers will be submitted to experimental pain and on the 2 study days receive Oxycodone 20 mg po vs. placebo. Half of the volunteers will be poor metabolizers according to CYP2D6 genotype and half will be extensive metabolizers (EM) and have an enzyme with normal function. The study hypothesis is that PM will experience less pain relief than EM.

NCT00271973 Healthy Drug: Oxycodone

Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. --- A118G ---

Primary Outcomes

Measure: Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.

Secondary Outcomes

Measure: The above compared to SNPs. Plasma levels of oxycodone and metabolites.

4 OPRM1 A118G SNP, Alcohol Response, and Striatal Dopamine

This study will examine the relationship between variations in a gene called OPRM1 and the response to alcohol. The OPRM1 (Mu-opioid Receptor-1) gene helps regulate brain pathways involved in experiencing pleasure. Brain pathways use a chemical called dopamine. Different forms of the OPRM1 gene may lead to differences in how dopamine is released and subsequently to differences in a person's response to alcohol. Healthy non-smokers between 21 and 45 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history and physical examination, blood and urine tests, and breathalyzer (breath alcohol test). A blood test is also done to determine the variant of OPRM1 gene. Participants undergo the following procedures in three study sessions: Session 1 " Breathalyzer test, urine test for illicit drugs and pregnancy test for women who can become pregnant. " Insertion of catheters (plastic tubes) into a vein in one arm for infusing alcohol and into the other arm for drawing blood samples. " Completion of questionnaires on how intoxicated the subject feels. " Blood draw for research studies. " Eye movement test (a visor with a digital camera tracks the subject's eye movements while he or she watches lights on a computer screen). " 45-minute alcohol infusion (up to 0,08 grams per deciliter - a level considered in most states as driving under the influence of alcohol). " Repeat breathalyzer, questionnaires, eye movement test and blood draw every 15 minutes during the infusion and again after the infusion is complete. " Subjects remain in the clinic until their blood alcohol content falls below 0.02 g/dL, determined by a breathalyzer test done every 15 minutes. Subjects can usually return home about 3 to 4 hours after the alcohol infusion stops. Sessions 2 and 3 The procedure is the same as for session 1, except subjects receive an infusion of alcohol one session and an infusion of saline (salt water) the other. Also, subjects undergo positron emission tomography (PET) scanning during the infusions. For this test, the subject lies on a bed that slides in and out of a doughnut-shaped scanner. A custom-molded mask is used to support the head and prevent it from moving during the scanning. A small amount of radioactive substance called C-11 raclopride is injected through one of the catheters to trace brain dopamine activity. ...

NCT00401999 Alcoholism
MeSH: Alcoholism

OPRM1 A118G SNP, Alcohol Response, and Striatal Dopamine. --- A118G ---

OPRM1 A118G SNP, Alcohol Response, and Striatal Dopamine This study will examine the relationship between variations in a gene called OPRM1 and the response to alcohol. --- A118G ---

A functional mu-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) alters the affinity of the mu-opioid receptor for its endogenous ligand, is in some studies associated with increased risk for alcohol and heroin addiction, and confers differential pain sensitivity and subjective responses to alcohol. --- A118G ---

This prompts the question whether the differential subjective response to alcohol observed as a function of the OPRM1 A118G genotype reflects differential activation of the mesolimbic DA release. --- A118G ---

The objective of this study is to examine the role of the A118G OPRM1 polymorphism for responses to a highly standardized intravenous alcohol challenge, with regard to psycho-physiological variables measured in the laboratory, and for brain dopamine release measured by 11C raclopride PET. --- A118G ---


5 Mu-Opioid Receptor Genetic Polymorphism and the Duration of Intrathecal Fentanyl Labor Analgesia. Mu-Opioid Receptor Genetic Polymorphism and the Efficacy of Postoperative Intrathecal Morphine Analgesia

Pharmacogenetics has allowed clinicians to identify associations between an individual's genetic profile and his/her response to drugs. The A118G (c.188A>G)is a single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1). The mutated protein, N40D, appears to increase the binding affinity and potency of beta-endorphin approximately 3-fold. Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by beta-endorphin action at the altered OPRM1. Combined spinal-epidural (CSE) analgesia is a commonly utilized technique for labor analgesia. Analgesia is initiated with the intrathecal administration of a lipid-soluble opioid (e.g. fentanyl), sometimes combined with a local anesthetic. The mean (± SD) duration of analgesia after intrathecal fentanyl 25 microgram was 89 ± 43 min. The ED50 of intrathecal fentanyl for labor analgesia varies between 14 microgram to 18.2 microgram. The wide variability in the duration of analgesia, as was well the differences in ED50 may result from differences known to affect labor pain (e.g., ethnicity, parity, stage of labor). Another possible explanation for the differences in opioid requirements and duration, as well as incidence of side effects such as itching and nausea/vomiting, is that opioid responsiveness is determined by genetic variability of the µ-opioid receptor. The ED50 for intrathecal fentanyl labor analgesia was significantly lower for parturients carrying the A118G variant of the mu-opioid receptor, compared to parturients with the A118 wild type receptor. The purpose of this study is to determine whether polymorphism at nucleotide 118 of OPRM1 influences the duration of intrathecal opioid (fentanyl) labor analgesia, and intrathecal opioid (morphine) postoperative analgesia.

NCT00418015 Labor Pain Post-cesarean Delivery Procedure: Blood Draw
MeSH: Labor Pain

The A118G (c.188A>G)is a single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1). --- A118G ---

Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by beta-endorphin action at the altered OPRM1. --- A118G ---

The ED50 for intrathecal fentanyl labor analgesia was significantly lower for parturients carrying the A118G variant of the mu-opioid receptor, compared to parturients with the A118 wild type receptor. --- A118G ---

SNP genotyping: For identification of allelic distribution of the A118G SNP, 20-60 ng of DNA from individuals will be first amplified by PCR (on thermocycler apparatuses equipped with a 96 well-microtiter plate block) using primers designed in the vicinity of the SNPs. --- A118G ---

Primary Outcomes

Description: Time from intrathecal drug administration to request for analgesia either in laboring women of after cesarean delivery

Measure: Duration of Intrathecal Fentanyl Analgesia

Time: Time (0-1440 minutes) to first analgesia request

Description: Time until request for supplemental analgesia following intrathecal morphine/fentanyl for cesarean delivery

Measure: Duration of Intrathecal Analgesia Following Cesarean Delivery

Time: 0 to 72 hours following cesarean delivery

Description: Visual analog pain scale (0 to 100) at 1st request for supplemental analgesia

Measure: Visual Analog Pain Scale (0 to 100) at Analgesia Request Following Intrathecal Intervention

Time: VAS at analgesia request

Secondary Outcomes

Description: Severity of pruritus during labor analgesia

Measure: Severity of Pruritus Following Fentanyl

Time: Labor analgesia

Description: Subjects reporting pruritus in the first 24 hours post cesarean delivery

Measure: Subjects With Pruritus at 24 Hours Post Morphine

Time: 24 hours post cesarean delivery

6 Effects of Smoking on Opioid Receptor Binding Using [(11)C]Carfentanil: An Imaging PET Study

Background: - Tobacco smoking is one of the most preventable causes of morbidity and mortality in the world, but the addictive property of nicotine is such that fewer than 10 percent of people who attempt to quit smoking remain tobacco-free after 1 year. Researchers are studying the addictive properties of nicotine in an attempt to develop more successful medication therapies for smoking cessation. - Nicotine acts on chemical receptors in the brain, including opioid receptors that affect the perception of pain. Repeated nicotine administration can cause adaptations in the brain s opioid receptors, which heightens the addictive properties of nicotine and increases the likelihood and severity of withdrawal symptoms associated with smoking cessation. Researchers are interested in using positron emission tomography (PET) scanning to study brain chemical responses to nicotine in current smokers and nonsmokers. Objectives: - To study brain chemical activity related to cigarette smoking and nicotine administration. - To compare the brain chemical activity of current daily smokers with that of nonsmokers. Eligibility: - Individuals 21 to 50 years of age who are either current smokers (10 to 25 cigarettes daily for at least 2 years) or have had some exposure to tobacco but have never smoked regularly (may have had a maximum of 20 cigarettes in their lifetime and none in past year). Design: - Eligible participants will undergo initial medical and psychological screening and neuropsychological testing before beginning the main phase of the study. Participants will be required to abstain from alcohol and drugs (except caffeine, nicotine, and prescription drugs) for 24 hours before each session, and smokers will refrain from smoking after midnight on the night before each session. - Session 1: Participants will answer questions about nicotine craving and withdrawal symptoms, followed by a magnetic resonance imaging (MRI) scan to provide baseline information about brain activity. - Session 2 and 3: Participants will answer questions about nicotine craving and withdrawal symptoms, and then will smoke one cigarette (either active nicotine or placebo). Researchers will document participants consumption of the cigarette. After the cigarette is smoked, participants will have a PET scan. Blood samples will be drawn during the PET session.

NCT00618631 Substance-related Discorder Drug: Nicotine Drug: Carfentanil

Outcome Measures: 1) displacement [(11)C]carfentanil binding, secondary to the release of endorphins by nicotine; 2) upregulation of [(11)C]carfentanil specific binding in smokers compared with nonsmokers; 3) [(11)C]carfentanil specific binding as a function of the mu-opioid receptor A118G polymorphism; and 4) correlation between self-report measures of nicotine effect and [(11)C]carfentanil binding profile. --- A118G ---

Primary Outcomes

Measure: Changes in carfentanil binding.

Secondary Outcomes

Measure: Cardiovascular and subjective responses to smoking one cigarette.

7 Defining an Endopheneotype for Alcohol Treatment With Naltrexone

This is a study involving treatment for alcohol dependence among males of European or Asian decent. The ultimate aim of this line of investigation is to further establish a genetic link between alcohol dependence and treatment by defining an endophenotype associated with treatment response. The study consists of two inpatient alcohol challenge sessions with treatment using random assignment to either naltrexone or placebo.

NCT00817089 Alcoholism Drug: Placebo Oral Tablet Drug: Naltrexone
MeSH: Alcoholism

Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. --- A118G ---

To further consolidate our knowledge, we wish to test the relationship between A118G polymorphism and the subjective/objective measures to alcohol among alcoholics treated with naltrexone. --- A118G ---

This work is focused on subjects of European or Asian decent as the A118G polymorphism occurs in less than 1% of those of African decent. --- A118G ---

Primary Outcomes

Description: Change from baseline to peak cortisol response, during the 2nd alcohol challenge session, subjective response as measured by Biphasic Alcohol Effects Scale: Total Mood. Biphasic Alcohol Effects Scale: Total Mood: minimum = 0, maximum = 106, higher scores indicate better outcomes.

Measure: Biphasic Alcohol Effects Scale:Total Mood

Time: during 2nd alcohol challenge session

Secondary Outcomes

Description: Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH).

Measure: Adrenocorticotropic Hormone (ACTH) Levels

Time: during 2nd alcohol challenge session

8 Pharmacogenetic Response to Naltrexone for Alcohol Dependence

The aims of the study are to test for treatment outcome differences in alcohol dependent subjects randomly assigned to 12 weeks of treatment with NTX (50mg/day) or placebo among those with one or two copies of the Asp40 allele of the mu-opioid receptor compared to those homozygous for the Asn40 allele. Thus, the design of the study is a 2X2 cell double-blind randomization to NTX or placebo stratified by genotype. To meet these aims, 150 alcohol dependent outpatients with one or two copies of the Asp40 variant of the mu-opioid receptor and 190 subjects homozygous for the Asn40 variant will be recruited across the four participating sites.

NCT00831272 Alcohol Dependence Drug: naltrexone Drug: Placebo
MeSH: Alcoholism

Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. --- A118G ---

To further consolidate our knowledge, we wish to test the relationship between A118G polymorphism and the response to treatment with naltrexone. --- A118G ---

This work is focused on subjects of European or Asian descent as the A118G polymorphism occurs in less than 1% of those of African descent. --- A118G ---

Primary Outcomes

Measure: Clinical Response to Naltrexone, as Measured by a Reduction in the Percent Days of Heavy Drinking Days (as Defined by >5 Drinks/Day for Males; >4 for Females) During the 12 Weeks of the Trial.

Time: 12 weeks

9 Sensitivity to Intravenous Nicotine: Genetic Moderators

To determine if the mu opioid receptor gene (OPRM1) A118G polymorphism moderates the subjective-rewarding effects of intravenous (IV) nicotine in male and female smokers. The subjective effects of nicotine will be measured with a Drug Effects Questionnaire, including the ratings of "good effects" and "drug liking". We hypothesize that smokers with the AG/GG genotype for the OPRM1 A118G will have attenuated subjective-rewarding effects from IV nicotine when compared to those with AA genotype.

NCT00969137 Nicotine Dependence Drug: saline Drug: Nicotine
MeSH: Tobacco Use Disorder

Sensitivity to Intravenous Nicotine: Genetic Moderators To determine if the mu opioid receptor gene (OPRM1) A118G polymorphism moderates the subjective-rewarding effects of intravenous (IV) nicotine in male and female smokers. --- A118G ---

We hypothesize that smokers with the AG/GG genotype for the OPRM1 A118G will have attenuated subjective-rewarding effects from IV nicotine when compared to those with AA genotype. --- A118G ---

primary hypotheses will test the influence of OPRM1 A118G status on subjective responses to IV nicotine, which will be measured with the drug effects questionnaire (DEQ).. null. --- A118G ---

Further, the functional OPRM1 A118G variant has been linked to rewarding effects of alcohol in alcohol users and to nicotine in female smokers. --- A118G ---

Since no previous studies examined the influence of the A118G variation on pure nicotine responses, the next logical step is to evaluate how this genetic polymorphism affects nicotine's rewarding, cognitive, and physiological effects using IV nicotine administration in male and female smokers. --- A118G ---

Primary Outcomes

Measure: primary hypotheses will test the influence of OPRM1 A118G status on subjective responses to IV nicotine, which will be measured with the drug effects questionnaire (DEQ).

Time: Injections 30 minutes apart

10 A Pilot Trial of Naltrexone for Methamphetamine Addiction - Role of the A118G SNP

The purpose of this study is to determine whether methamphetamine-dependent individuals will use less methamphetamine when treated with naltrexone. The study will also investigate whether individuals with the mu opioid receptor gene variant A118G will use less methamphetamine than individuals without A118G.

NCT00984360 Methamphetamine Dependence Drug: Naltrexone
MeSH: Behavior, Addictive
HPO: Addictive behavior

A Pilot Trial of Naltrexone for Methamphetamine Addiction - Role of the A118G SNP. --- A118G ---

The study will also investigate whether individuals with the mu opioid receptor gene variant A118G will use less methamphetamine than individuals without A118G. --- A118G ---

The study will also investigate whether individuals with the mu opioid receptor gene variant A118G will use less methamphetamine than individuals without A118G. --- A118G --- --- A118G ---

Primary Outcomes

Measure: MA (-) Urine Samples

Time: Twice weekly for 5 weeks

11 Functional Characterization of OPRM1 A118G in Nicotine Dependence: IV Nicotine Study

A substantial body of evidence implicates the endogenous opioid system, and the mu opioid receptor (MOR) in particular, in the reinforcing effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the mu opioid receptor gene (OPRM1 Asp40) is associated with the ability to quit smoking, as well as nicotine reward and withdrawal symptoms. However, the precise mechanism through which this SNP influences nicotine dependence remains unresolved. This positron emission tomography (PET) study will examine whether this OPRM1 SNP alters MOR binding in response to nicotine in human smokers. Specifically, we will use [11 C]carfentanil PET imaging to assess the effects of intravenous (IV) nicotine versus saline (within-subject) on MOR binding potential in 24 chronic smokers genotyped prospectively and stratified by OPRM1 genotype.

NCT01040338 Nicotine Dependence Drug: Nicotine
MeSH: Tobacco Use Disorder

Functional Characterization of OPRM1 A118G in Nicotine Dependence: IV Nicotine Study. --- A118G ---

Primary Outcomes

Measure: MOR binding potential

Time: 5/31/2011

Secondary Outcomes

Measure: Subjective reward/liking and cravings to smoke

Time: 5/31/2011

12 CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk

The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.

NCT01050400 Cytochrome P450 2D6 Ultra-rapid Metabolism Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.
MeSH: Drug-Related Side Effects and Adverse Reactions

Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment.. null. --- A118G ---

Primary Outcomes

Measure: Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population

Time: 5-8 days post c-section surgery

Secondary Outcomes

Measure: Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios.

Time: Minimum 1 week prior to c-section

Measure: Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment.

Time: Minimum 1 week prior to c-section

Measure: Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment.

Time: Minimum 1 week prior to c-section

13 Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain

Drug therapy in patients with chronic low back pain is a major challenge for physicians. One of the problems is the lacking knowledge in prediction of drug efficacy in a chosen patient. Usually one of the classes of pain medication is given to patients with a similar clinical picture, although different pain mechanisms may be responsible for this clinical picture. Another reason for variable drug efficacy are genetic polymorphisms, this may be the reason why an unique drug produces different responses (from a lacking analgesic effect up to excessive effect or side-effects. Quantitative sensory testing is a method that documents alterations in the pain perception system. Linking genetic polymorphisms to quantitative sensory testing may give us a tool for anticipation of drug efficacy.

NCT01179828 Low Back Pain Drug: Oxycodone 15mg Drug: Clobazam Drug: Imipramine Drug: Tolterodine
MeSH: Back Pain Low Back Pain
HPO: Back pain Low back pain

Methods Quantitative sensory testing: Heat pain threshold and tolerance, Ice water testing with central modulation of nociceptive input (DNIC), electrical pain detection and temporal summation (skin probe), pressure algometry with pain detection and threshold Drugs investigated: Imipramine, Oxycodone, Clobazam Blood samples: pharmacogenetics: Cytochrome variants CYP2D6, CYP2C19, CYP3A4, COMT haplotypes, CGH-1 variants, A118G of mu opioid receptor gene variants pharmacokinetics: kinetics of imipramine and desipramine --- A118G ---

Primary Outcomes

Measure: Difference in NRS(pain scale) between measurement after and before drug administration

Time: 07/2012

Secondary Outcomes

Measure: Patients global impression of change scale after drug administration

Time: 07/2012

Measure: Pharmacogenetic variables(see before)

Time: 07/2012

Measure: Pharmacokinetics: measure of Imipramine and desipramine blood levels

Time: 07/2012

Measure: Reliability of repeated quantitative sensory testing in the same patient

Time: 12/2010

14 Association Between Clinical Effect of Continuous Morphine Administration in Patients After Major Surgery and Pharmacogenetics: Perspective Observational Clinical Study

Identification of the genetic polymorphisms that could be correlated either with a better clinical response or with a major predisposition of patients to develop tolerance and/or side effects to the treatment with morphine.

NCT01233219 Anesthesia Surgery Drug: morphine chlorhydrate

Assessment of the rescue doses in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele. --- A118G ---

Valuation of the rescue doses necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).. Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure. --- A118G ---

- Allergies to morphine and derivates Anesthesia Surgery Valuation of the rescue doses necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%). --- A118G ---

Primary Outcomes

Description: Valuation of the rescue doses necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).

Measure: Assessment of the rescue doses in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele

Time: first 24 h after surgery

Secondary Outcomes

Description: Frequency of the variants at the loci OPRM1, COMT, UGTs, ESR1, both in patients with NRS ≤4 and in those having NRS >4 at least once during 24 hours.

Measure: Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure

Time: during 24 h postsurgery

Description: Frequency of the variants at the loci OPRM1, COMT, UGTs, ESR1, both in patients with NRS ≤4 and in those having NRS >4 at least once during the period between 24-48 hours postsurgery.

Measure: Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure

Time: period between 24 - 48 h postsurgery

Description: Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).

Measure: Pharmacokinetics of morphine during continuous administration after surgery

Time: 48 h after surgery

Description: Detection of the possible side effects after continuous morphine administration

Measure: Detection of the possible side effects.

Time: 72 h postopratively

Description: Detection of the association between M3G/M6G ratio and polymorphisms of UGTs and its possible side effects.

Measure: Detection of the association between M3G/M6G ratio and polymorphisms of UGTs

Time: within 72 h postoperatively

15 Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study.

Identification of the genetic polymorphisms that could be correlated either with a better clinical response or with a major predisposition of patients to develop tolerance and/or side effects to the treatment with morphine.

NCT01233752 Anesthesia Surgery Drug: morphine chlorhydrate

Assessment of the medium morphine dose (mg/kg/die)in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele. --- A118G ---

Valutation of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).. Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure. --- A118G ---

- Allergies to morphine and derivates Anesthesia Surgery Valuation of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%). --- A118G ---

Primary Outcomes

Description: Valutation of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).

Measure: Assessment of the medium morphine dose (mg/kg/die)in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele

Time: first 24 h after surgery

Secondary Outcomes

Description: Frequency of the variants at the loci OPRM1, COMT, UGTs, ESR1, both in patients with NRS ≤4 and in those having NRS >4 at least once during 24 hours.

Measure: Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure

Time: during 24 h postsurgery

Description: Detection of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 though the first 48 hours after surgery.

Measure: Detection of the medium morphine dose

Time: First 24 h after surgery

Description: Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).

Measure: Pharmacokinetics of morphine with PCA after surgery

Time: 48 h after surgery

Description: Variants frequency at loci OPRM1, COMT, UGTs, ESR1 in the patients with Cmax and AUC of both morphine and M3G-M6G metabolites >2 standard deviations higher than expected population curve ("outliers").

Measure: Variants frequency at loci OPRM1, COMT, UGTs, ESR1

Time: Within 48h after surgery

Measure: Detection of the possible side effects.

Time: 72 h postopratively

Measure: Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects).

Time: within 72 h postoperatively

16 Pain Sensitivity in Acute Inflammatory Pain - Gender Differences and Validity of Sensory Tests

Pain is a complex experience influenced by gender and genetics, and, by psychosocial and sensory experiences. Pain sensitivity is thus highly variable between individuals. In the present study we evaluate individuals´ pain perception in response to a number of different pain stimuli in 100 healthy volunteers (50 females and 50 males). The data will allow us to assess pain sensitivity, to predict pain responses and to investigate gender related differences in pain perception. A second aim is to evaluate the robustness of the different pain-tests since the tests are repeated with an interval of 2-4 weeks.

NCT01345877 Healthy Volunteers Are Studied Procedure: first degree cutaneous burn injury
MeSH: Hypersensitivity
HPO: Allergy

A118G SNP. --- A118G ---

Psychophysical assessments following induction of a first degree burn injury (47.0 C, 420 s, 12.5 sq.cm, lower leg) include: - pain during induction of burn injury - thermal thresholds - tactile thresholds - electrical thresholds - areas of secondary hyperalgesia - pressure algometric assessments - assessment of Diffuse Noxious Inhibitory Control (DNIC) efficiency - assessment of (DNIC) using cold pressor test Psychological assessments include: - HADS (Hospital Anxiety and Depression Scale) - PCS (Pain Catastrophizing Scale) - vulnerability score Genetics include: - A118G SNP Demographics include: - gender - height - weight --- A118G ---

Primary Outcomes

Measure: pain following burn injury

Time: from baseline to 420 s after burn injury

Secondary Outcomes

Measure: thermal thresholds

Time: followed for 180 min after burn injury

Measure: tactile thresholds

Time: followed for 180 min after burn injury

Measure: pressure algometry assessments

Time: 95 min prior to burn injury

Measure: DNIC-efficiency

Time: 45 min before burn injury

Measure: cold pressor test

Time: 85 min before burn injury

Measure: HADS score

Time: 2 hours before the burn injury

Measure: PCS ratings

Time: 2 hours before the burn injury

Measure: A118G SNP

Time: 8 months after inclusion completed

17 Pharmacogenetics of Remifentanil in Patients With Hypertension Undergoing Cesarean Delivery Under General Anesthesia

Caesarean delivery under general anaesthesia (GA) carries nowadays still 25% risk of insufficient depth of anaesthesia in a time before the fetus delivery. The reason is the lack of opioid administration. Opioids easily cross placental barrier and negatively influence newborn postpartum adaptation by respiratory depression. Introduction to GA is thus accompanied by exaggerated autonomic stress reaction with hypertension and tachycardia. The use of ultra-short acting opioid remifentanil should suppress stress response in mother without increasing the risk for newborn. There are only a few clinical data available. This study will be the first one systematically studying the influence of remifentanil in pregnant women with hypertension on hemodynamic stability and newborns safety. This study will also identify potential pharmacogenetic factors of individual variability in remifentanil response with respect of drug efficacy and safety in mother and newborn.

NCT01550640 Pregnancy Cesarean Delivery General Anesthesia Drug: Remifentanil
MeSH: Hypertension
HPO: Hypertension

Method for assessment of opioid receptor polymorphism (A118G) will be implemented during the first year of the study. --- A118G ---

Primary Outcomes

Description: newborn status (Apgar score + acid-base measurement from umbilical cord, clinical evaluation and scoring)

Measure: Newborn adaptation after delivery

Time: 10 min after delivery

Measure: Influence of individual hereditary variability in MDR1 (multidrug resistance gene 1) and PXR (pregnane X receptor) on remifentanil pharmacodynamics.

Time: at time of delivery

Secondary Outcomes

Description: BIS (continuous bispectral EEG analysis)

Measure: Depth of anesthesia

Time: 30 min from induction to general anesthesia

Description: Changes in major hemodynamic parameters (Systolic Blood Pressure, Heart Rate, ST analysis)

Measure: Hemodynamic response to intubation and beginning of Cesarean operation

Time: 30 min from induction to general anesthesia

18 A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Influence of the A118G Polymorphism in the mu Opioid Receptor Gene (OPRM1) on Effects of GSK1521498 and Naltrexone on Physiological and Behavioural Markers of Brain Function in Healthy Social Drinkers

A total of at least 48 healthy subjects with a history of social drinking will be recruited into this single-centre, randomized, double-blind, cross-over study. Subjects will be genetically stratified to result in equal numbers of A118G 'AA' homozygotes (n=24) and A118G 'G' carriers (n=24). Subjects will participate in all three treatment periods and will be randomized to receive each of the following for 5 days: Treatment A: Placebo, Treatment B: Naltrexone (NTX) 50 mg once daily (25 mg once daily for the first two days) and Treatment C: GSK1521498 10 mg once daily. A washout period will be of at least 14 days between treatments. Subjects will return for a follow-up visit 7-10 days after the final treatment session washout period has been completed. Subjects will attend the clinical research unit on days 1, 2, 3, 4 and 5 to monitor safety and tolerability for both drugs. Subjects will attend the clinical unit on days 4 and 5 for a two day assessment, using a series of pharmacodynamic measurements known to be sensitive to the effects of GSK1521498 and/or NTX: Functional brain response to alcohol and food cues; plasma cortisol; hedonic and consummatory eating behaviors; subjective response to an ethanol challenge; experimental pain threshold; and cognitive tests of attention bias towards alcohol and food cues.

NCT01738867 Alcoholism Drug: GSK1521498 Drug: Naltrexone (NTX) Drug: Placebo
MeSH: Alcoholism

A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Influence of the A118G Polymorphism in the mu Opioid Receptor Gene (OPRM1) on Effects of GSK1521498 and Naltrexone on Physiological and Behavioural Markers of Brain Function in Healthy Social Drinkers. --- A118G ---

To Evaluate the Influence of the A118G Polymorphism in the mu Opioid Receptor Gene (OPRM1) on Effects of GSK1521498 and Naltrexone on Physiological and Behavioural Markers of Brain Function in Healthy Social Drinkers A total of at least 48 healthy subjects with a history of social drinking will be recruited into this single-centre, randomized, double-blind, cross-over study. --- A118G ---

Subjects will be genetically stratified to result in equal numbers of A118G 'AA' homozygotes (n=24) and A118G 'G' carriers (n=24). --- A118G ---

Subjects will be genetically stratified to result in equal numbers of A118G 'AA' homozygotes (n=24) and A118G 'G' carriers (n=24). --- A118G --- --- A118G ---

To test that the OPRM1 A118G polymorphism modulates the effects of GSK1521498 10 mg on brain reward function and processing. --- A118G ---

Plasma cortisol concentrations will be measured under fasting conditions to test that the OPRM1 A118G polymorphism modulates the effect of GSK1521498 10mg on plasma cortisol. --- A118G ---

Primary Outcomes

Description: To test that the OPRM1 A118G polymorphism modulates the effects of GSK1521498 10 mg on brain reward function and processing

Measure: Brain activation within the reward circuitry in response to consumption of food and alcohol cues, as measured by functional magnetic resonance imaging (fMRI)

Time: Day 5 in each treatment period

Description: Number of subjects with any adverse events during the treatment periods

Measure: Adverse events as a measure of safety and tolerability

Time: Throughout the study, from Day 1 to Day 67

Description: Systolic and diastolic BP will be measured

Measure: Blood pressure (BP) as a measure of safety and tolerability

Time: Screening (Up to 30 days prior to Day 1), Day 1, Day 2, Day 5 in each treatment period and Follow-up visit.

Description: 12-lead electrocardiograph (ECG) will be measured

Measure: 12-lead ECG and heart rate as a measure of safety and tolerability

Time: Screening (Up to 30 days prior to Day 1), Day 1, Day 2, Day 5 in each treatment period and Follow-up visit.

Description: Hematology/Chemistry assessments to be done at screening (fasted) and day 5 for each treatment session (un-fasted).

Measure: Clinical chemistry including liver enzymes and hematology as a measure of safety and tolerability

Time: Screening (Up to 30 days prior to Day 1), Day 5 of each of the 3 treatment periods and Follow-up visit

Description: Mood anxiety will be assessed by The Beck Anxiety Inventory (BAI), The Beck Depression Inventory (BDI-II).

Measure: Psychiatric symptom questionnaires-Becks Depression & Anxiety Inventory (BDI-II & BAI)

Time: Screening (Up to 30 days prior to Day 1), Day 1 (pre-dose and approximately 4 hours post dose), Day 2 (prior to discharge), Day 3 (prior to discharge), Day 5 (prior to discharge), in each treatment period and Follow-up visit

Description: Suicidality will be assessed by C-SSRS.

Measure: Psychiatric symptom questionnaires- Columbia Suicide Severity Rating Scale (C-SSRS)

Time: Screening (Up to 30 days prior to Day 1), Day 1 (pre-dose and approximately 4 hours post dose), Day 2 (prior to discharge), Day 5 (prior to discharge), in each treatment period and Follow-up visit

Description: Mood anxiety and suicidality will be assessed by VAS.

Measure: Psychiatric symptom questionnaires- Bond and Lader Visual Analogue Scales (VAS).

Time: Screening (Up to 30 days prior to Day 1), Day 1 (pre-dose and approximately 4 hours post dose), Day 2 (prior to discharge), Day 3 (prior to discharge), Day 4 (prior to discharge), Day 5 (prior to discharge), in each treatment period and Follow-up visit

Description: CANTAB attention tasks comprising of Simple Reaction Time (SRT), Choice Reaction Time (CRT) and Rapid Visual Information Processing (RVP) will be done to measure the power of attention

Measure: Computerized tests of reaction time (CANTAB)

Time: Approximately 1 hour pre-dose on Day 1 and approximately 4 hours post dose on Day 1, Day 2 and Day 5 in each treatment period

Secondary Outcomes

Description: Plasma cortisol concentrations will be measured under fasting conditions to test that the OPRM1 A118G polymorphism modulates the effect of GSK1521498 10mg on plasma cortisol

Measure: Plasma cortisol concentrations

Time: Day 1 and Day 5 pre-dose, at approximately the same time, and on Day 5 post dose in each treatment period.

Description: Pressure pain threshold and sensitivity will be measured in response to cutaneous pressure. Pressure pain thresholds and tolerance will be assessed at two tender points (left and right trapezius points, as defined by American College of Rheumatology)

Measure: Pressure pain threshold and sensitivity

Time: Day 4 in each treatment period.

Description: Eating behaviour will be assessed by ad libitum snacking , Menu choices and ad libitum intake of test buffet meals, Appetite Visual Analogue Scales (A-VAS) and Binge Eating Scale (BES)

Measure: Consummatory eating behaviour

Time: Day 5 in each treatment period.

Description: Response to sweet and high fat samples (tasting sweetened dairy products), will be performed in a fasted state. The Hedonic 9 point preference scale and Sensory Stimuli Scale will be performed after each sample has been tasted.

Measure: Hedonic taste preference

Time: Day 5 in each treatment period.

Description: It will be measured using self-report questionnaires Biphasic alcohol effects scale (BAES), Subjective High Assessment Scale (SHAS), Profile of Mood States (POMS-B), and Alcohol Rating Scale (ARS)

Measure: Subjective responses to intravenous doses of ethanol

Time: Day 4 in each treatment period

Description: The comparison will be done for the all efficacy endpoints as mentioned earlier which include Plasma cortisol; fMRI and cognitive measures of reward processing; pain threshold; hedonic and consummatory eating behaviour, subjective response to ethanol

Measure: To compare the placebo-controlled effects of GSK1521498 10 mg to the placebo-controlled effects of NTX 50 mg

Time: Day 5 in each treatment period.

19 OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate

Background: - Small differences in genes may alter responses to drugs. One gene that has different forms is the mu opioid receptor gene. People with one form of this gene are more sensitive to alcohol. People with a different form are sometimes more sensitive to pain. Morphine and other prescription pain pills produce pain relief by acting at the mu opioid receptor. Researchers want to see the effect of morphine on brain reward and subjective effects. Morphine is a strong but short-acting pain medication that is sometimes used for anesthesia during surgery. Objectives: - To compare the effect of morphine on brain measures of dopamine release using imaging. Eligibility: - Individuals between 21 and 55 years of age who have previously taken pain pills prescribed to treat pain from a medical or dental procedure. Design: - This study has a screening phase and a study phase. The screening phase involves one or two visits of 5 to 6 hours. The study phase consists of 4 study visits. Each study visit will take about 8 hours. - Participants will be screened with a medical and psychiatric history and physical exam. They will be asked about drinking and drug-taking history, and any family history of alcoholism or drug abuse. Blood, urine, and breath samples will be collected. - During the first study visit, an MRI scan may be performed, questionnaires completed, and a blood sample collected for genetic testing. - During study visit 2, participants will test their pain sensitivity by placing one hand in cold water. Pupil diameter will be measured after the sensitivity test. After a blood sample is taken, participants will receive the morphine or a salt solution. The sensitivity test and pupil diameter test will be repeated. Final blood samples will be collected. A brief physical exam will also be performed. - During study visits 3 and 4, participants will receive morphine or a salt solution during a PET scan. Questionnaires to assess subjective effects will be administered. Final blood samples will be collected. A brief physical exam will also be performed. - Participants will stay in the clinic until the effects of the drug have worn off after study visits 2, 3, and 4. - About 1 week after the study session, participants will have a follow-up phone call.

NCT01878006 Polymorphism-Genetic Pain Addiction Drug: Morphine Drug: Placebo
MeSH: Behavior, Addictive
HPO: Addictive behavior

OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate. --- A118G ---

A functional µ-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) has been associated with increased risk for heroin addiction in some studies. --- A118G ---

The objective of this study is to examine the role of the A118G OPRM1 polymorphism for responses to a challenge of an opiate (morphine) with regard to psycho-physiological variables measured in the laboratory and for brain dopamine release measured by [11C]raclopride PET. --- A118G ---

Primary Outcomes

Description: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Measure: 11C Raclopride Binding Potential in Caudate

Time: 90 minutes following injection

Description: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Measure: 11C Raclopride Binding Potential in Nucleus Accumbens

Time: 90 minutes following injection

Description: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Measure: 11C Raclopride Binding Potential in Putamen

Time: 90 minutes following injection

Description: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Measure: 11C Raclopride Binding Potential in Ventral Pallidum

Time: 90 minutes following injection

Secondary Outcomes

Description: Area under the curve of the subjective perception-time course - Feel Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.

Measure: Subjective Perception of Morphine Effect - Feel Drug

Time: 60 minutes following injection

Description: Area under the curve of the subjective perception-time course - Feel High. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.

Measure: Subjective Perception of Morphine Effect - Feel High

Time: 60 minutes following injection

Description: Area under the curve of the subjective perception-time course - Like Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.

Measure: Subjective Perception of Morphine Effect - Like Drug

Time: 60 minutes following injection

Description: Area under the curve of the subjective perception-time course - Want More. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.

Measure: Subjective Perception of Morphine Effect - Want More

Time: 60 minutes following injection

20 Optimizing Naltrexone for Individuals of East Asian Descent

This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of East Asian descent, an ethnic group most likely to express the positive predictive allele.

NCT02026011 Alcohol Use Disorder Drug: Naltrexone Drug: Placebo
MeSH: Alcoholism Alcohol Drinking

Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Alcohol Use Disorder Alcoholism Alcohol Drinking Recent pharmacogenetic studies have advanced the gene coding for µ-opioid receptors (OPRM1) gene as a potential moderator of responses to naltrexone. --- A118G ---

Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Alcohol Use Disorder Alcoholism Alcohol Drinking Recent pharmacogenetic studies have advanced the gene coding for µ-opioid receptors (OPRM1) gene as a potential moderator of responses to naltrexone. --- A118G --- --- A118G ---

Primary Outcomes

Description: Alcohol Urge Questionnaire (AUQ) is used to assess subjective experiences of craving for alcohol. It consists of 8 items, each rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). A summary score is used at each assessment time point. The AUQ was administered at baseline and three levels of breath alcohol concentration: 0.02 g/dl. 0.04, g/dl, and 0.06 g/dl.

Measure: Subjective Response - Craving for Alcohol

Time: The AUQ was administered across a period of approximately 1.5 hours.

Description: The Biphasic Alcohol Effects Scale (BAES) Stimulant Subscale consists of 14 items designed to capture the stimulant effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the stimulant subscale ranges from 0-70.

Measure: Subjective Response - Stimulation

Time: The BAES Stimulant Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours

Description: The Biphasic Alcohol Effects Scale (BAES) Sedation Subscale consists of 14 items designed to capture the sedating effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the sedation subscale ranges from 0-70.

Measure: Subjective Response - Sedation

Time: The BAES Sedation Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours

Description: Alcohol taste cues task for functional magnetic resonance imaging (fMRI). Region of Interest (ROI) were atomically defined using the Harvard-Oxford atlas in standard Montreal Neurological Institute (MNI) space, which were transformed into individual participants' native space using Functional Magnetic Resonance Imaging of the Brain Software Library (FSL). Contrast estimates are for Alc > Water cue, and are arbitrary units.

Measure: Neural Response to Alcohol Cues

Time: During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes

Secondary Outcomes

Description: Total number of drinks consumed during the alcohol self-administration task

Measure: Alcohol Self-administration - Number of Drinks

Time: Alcohol self-administration period was 1 hour long

21 A Multi-site, Double-blind, Parallel Arm, Block Randomised, Placebo Controlled, Factorial Phase III Study of Opioids for Chronic Refractory Breathlessness in People With Chronic Obstructive Pulmonary Disease.

Breathlessness, the sensation of breathing discomfort, is a major problem in people with chronic obstructive pulmonary disease (COPD). Breathlessness that persists despite optimal management of the underlying disease(s) is said to be refractory. Preliminary evidence suggests that a small, regular dose of morphine helps to reduce safely the sensation of breathlessness. However, this research on morphine for breathlessness has not defined the best way to adjust the dose of the medication, or refined which people are most likely to have benefit, no response or side effects. This is a randomized, double-blind phase III trial in people with COPD and significant refractory breathlessness, which will explore several important questions: - Are regular, low dose opioids (morphine) at four possible doses over 3 weeks more effective than placebo medication (containing no active ingredient) at improving breathlessness? - Does the medication have any effect on daily activity, breathlessness, and quality of life? - What are the common side effects of this intervention? - Does the benefit from the drug outweigh the side effects it produces? - Are there specific characteristics of people who are more likely to receive benefit from sustained release morphine? Participants will be allocated to receive three weeks of morphine sulfate (and laxative, docusate with senna), or placebo (and placebo laxative). The dose of morphine may be increased each week for weeks two and three. All medicines will appear the same (blinded) and neither the doctor nor the participant will know which medication the participant is receiving. Participants will have a medical interview, physical examination to collect some general health information, and baseline measurements including; daily activity, symptoms, and quality of life. A small amount of blood may be required to check eligibility. Further blood samples may be taken at week 1 and 3 to enable testing on how individuals respond to opioids, further consent will be obtained for these samples. Data on benefits, side effects, and medical care will be collected during comprehensive weekly visits. Participants will also fill out a simple diary twice daily for weeks one to three of the study, and for one day each week during an optional 3 month extension stage. The outcome of this study may enable better management of symptoms and activity in people COPD with medicines that are shown to be effective and safe.

NCT02455362 Chronic Obstructive Pulmonary Disease Dyspnea Drug: Morphine sulfate Drug: Placebo
MeSH: Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Dyspnea
HPO: Abnormal lung morphology Chronic obstructive pulmonary disease Dyspnea Obstructive lung disease Respiratory distress

From the baseline sample, the UGT2B7*2 and *28 polymorphisms, P-glycoprotein (ABCB1 5SNPs in a haplotype block), the 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572, and mu opioid receptor (A118G) polymorphisms will be measured. --- A118G ---

Primary Outcomes

Description: Rated on a 0-10 numerical rating scale (NRS) in a diary each evening. The primary endpoint is the difference between placebo, morphine sulfate 8 mg, or 16 mg after the first treatment week.

Measure: Change from baseline intensity of breathlessness over the previous 24 hours

Time: Week 1

Secondary Outcomes

Description: Rated on a 0-10 numerical rating scale (NRS) in a diary each evening.

Measure: Change from baseline unpleasantness of breathlessness over the previous 24 hours

Time: Week 3

Description: Rated on a 0-10 numerical rating scale (NRS) in a diary each morning.

Measure: Change from baseline intensity of breathlessness "right now"

Time: Week 3

Description: In addition to the NRS ratings, the intensity of breathlessness is rated on a 0-10 modified Borg scale in a evening diary.

Measure: Change from baseline in the intensity of breathlessness

Time: Week 1

Description: Collected in a diary in the evening, including of any rescue medication used.

Measure: Current medication use and compliance

Time: At study end for up to 15 weeks.

Description: Collected in a diary in the evening.

Measure: Number of participants with adverse events

Time: At study end for up to 15 weeks.

Description: Measured during two days at baseline and during at least five days of treatment week three.

Measure: Change from baseline physical activity using an accelerometer

Time: Week 3

Description: Measured using the revised Edmonton Symptoms Assessment Scale (ESAS-r).

Measure: Change from baseline in concurrent symptoms

Time: Week 1

Description: Measures the functional impact of breathlessness.

Measure: The modified Medical Research Council (mMRC) breathlessness scale

Time: At study end for up to 15 weeks.

Description: To explore whether longer term morphine treatment is associated with decreased levels of testosterone.

Measure: Change from baseline serum testosterone level

Time: At the end of the 3 month follow-up stage, after up to 15 weeks.

Description: From the baseline sample, the UGT2B7*2 and *28 polymorphisms, P-glycoprotein (ABCB1 5SNPs in a haplotype block), the 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572, and mu opioid receptor (A118G) polymorphisms will be measured. Interleukin 1ß, TNFalpha and Il-6 will be measured at baseline and at the end of the first treatment week.

Measure: Change from baseline pharmacogenomic opioid blood profile

Time: Week 1

Description: In a subset of 55 participants, blood parameters for morphine and its metabolites will be analysed (4 blood samples over 8 hours) at steady state of the treatment at the end of the week 1.

Measure: Pharmacodynamic/-kinetic blood samples

Time: Week 1

Description: Exhaled gas measured using a non-invasive capnometer.

Measure: Change from baseline end-tidal carbon dioxide

Time: Week 3

Description: Non-invasive measurement of the oxygen saturation, respiratory rate, and heart rate.

Measure: Change from baseline pulse oximetry

Time: Week 3

Description: Twenty (20) participants at the Sydney and Adelaide sites will be invited to undertake a simple, non-invasive home sleep study using the ResMed ApneaLink Plus device.

Measure: Change from baseline sleep quality

Time: The final night of week 3

Description: Rated on a 4 point Likert scale in a morning diary.

Measure: Change from baseline sleep quality

Time: During the study for up to 15 weeks.

Description: The questionnaires used are the Epworth Sleepiness Scale, Leeds Sleep Questionnaire, and the Karolinska Sleepiness Scale.

Measure: Change from baseline sleep quality and sleep-related problems

Time: Week 3

Description: Measure of the bowel function, during treatment with placebo / morphine sulfate 8 or 16 mg.

Measure: Change from baseline bowel function index

Time: Week 1

Description: Measured on the CRQ-SAS Dyspnoea sub-scale.

Measure: Change from baseline breathlessness-related quality of life

Time: Week 3

Description: Measured using the EQ-5D questionnaire.

Measure: Change from baseline health-related quality of life

Time: During the study for up to 15 weeks.

Description: Life-Space is a measure of where a person goes, the frequency of going there, and the dependency in getting there.

Measure: Change from baseline Life-space

Time: During the study for up to 15 weeks.

Description: A score of 0 to 100 (in increments of 10) is assigned to participants based on their ability to undertake a range of daily tasks. The score gives an indication of the participant condition in terms of physical ability.

Measure: Change from baseline Australian Karnofsky Performance Status

Time: During the study for up to 15 weeks.

Description: A 14-item questionnaire used to measure anxiety and/or depression.

Measure: Change from baseline Hospital Anxiety and Depression Scale

Time: Week 3

Description: Participant-rated seven point scale of the perception of their change, specifically their improvement since the commencement of the study.

Measure: Global Impression of Change

Time: During the study for up to 15 weeks.

Description: Participants will be asked for their preference to continue at study exit ('Is this a therapy which, on balance, you would continue to take for your breathlessness?')

Measure: Blinded patient preference to continue treatment

Time: At study end after up to 15 weeks.

Description: Data on all health care contacts including lenght of hospitalizations, emergency department visits, DRG codes, outpatient visits to general practitioner and community nurse, and date of death.

Measure: Health economy composite

Time: During the study for up to 15 weeks.

22 Post-surgical Pain Assessment in Children: Roles of Skin Conductance and Genomics

Pain assessment in infants and toddlers is quite challenging since children in these populations are nonverbal or preverbal and cannot describe the presence and severity of pain that they perceive. Over the last decade, advances in the field have included the development of behavioral scoring systems for the assessment of acute pain . However, although they have been validated, these commonly used methods of pain assessment are largely subjective and rely on a highly trained observer. An objective continuous measure of pain would be an important addition to standard behavioral painscores which require nurses to monitor the child's behavioral responses.

NCT02534168 Pain Device: Skin conductance monitor for measuring skin conductance

The ability of skin conductance monitor to predict post-operative pain scores, sensitivity and specificity will be measured.. Effect of single nucleotide polymorphisms in the mu-opioid receptor A118G on post-operaive pain scores. --- A118G ---

Association of the mu-opioid receptor gene A118G polymorphisms with inter-individual differences in the pain scores with standardized treatments will be evaluated.. Inclusion Criteria: - Children 0 - 3 years of age inclusive - Presenting for palatal repair (palatoplasty) - American Society of Anesthesiologists (ASA) physical status of 1 or 2 Exclusion Criteria: - Children > 3 years of age - On chronic pain treatment - Pre-operative use of analgesics - Allergies to any anesthetics or analgesia products - Known obstructive sleep apnea - Diagnosis of Cystic fibrosis - American Society of Anesthesiologists (ASA) physical status ≥ 3 Inclusion Criteria: - Children 0 - 3 years of age inclusive - Presenting for palatal repair (palatoplasty) - American Society of Anesthesiologists (ASA) physical status of 1 or 2 Exclusion Criteria: - Children > 3 years of age - On chronic pain treatment - Pre-operative use of analgesics - Allergies to any anesthetics or analgesia products - Known obstructive sleep apnea - Diagnosis of Cystic fibrosis - American Society of Anesthesiologists (ASA) physical status ≥ 3 Pain After standard general anesthetic mask induction, 0.5 ml of blood will be drawn for genetic analysis when the intravenous catheter is sited. --- A118G ---

Primary Outcomes

Description: The skin conductance monitor will be attached to the patient in the Post-Anesthesia Care Unit (PACU) for 1 hour and the skin condutance values will be analyzed off-line. Corresponding pain scores on a scale of 0-10 using the FLACC (Face, Legs, Activity, Cry and Consolibility) scale will be noted every 5 minutes for a period of 1 hour. The skin conductance values will be measured in microsiemens, also the frequency of the skin conductance responses per second will be measured. The ability of skin conductance monitor to predict post-operative pain scores, sensitivity and specificity will be measured.

Measure: skin conductance measurements

Time: 2 years

Secondary Outcomes

Description: Association of the mu-opioid receptor gene A118G polymorphisms with inter-individual differences in the pain scores with standardized treatments will be evaluated.

Measure: Effect of single nucleotide polymorphisms in the mu-opioid receptor A118G on post-operaive pain scores

Time: 2 years

23 Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation

Background: Drugs like nalmefene interfere with opioid receptors. This might reduce drinking. The gene OPRM1 determines opioid receptor functions. Researchers want to see if nalmefene affects people s responses to alcohol cues. They also want to compare how nalmefene affects people with different forms of OPRM1. Objectives: To test nalmefene s effects on alcohol self-infusion and responses to alcohol cues. To test the role of different forms of OPRM1 on these effects. Eligibility: Healthy heavy drinkers ages 21 60: Women: over 15 drinks weekly Men: over 20 drinks weekly Design: Participants will be screened with: Medical history Physical exam Heart, blood, and urine tests Questionnaires Participants will have three 10-hour visits and one 2-hour follow-up visit. They will take a taxi. Visits are about 1 week apart. Before visits, participants cannot drink alcohol for 1 day or take medicine for 3 days. All study visits: Questionnaires Heart monitor Two-hour alcohol session: A needle guides a thin plastic tube into a vein in each arm. One tube receives alcohol. The other draws blood. Participants give themselves alcohol by pressing a button on a computer. Relaxing at the center until breath alcohol falls below 0.02 percent, or for 3 hours. Visits 2 and 3: Swallowing nalmefene or placebo. One-hour brain MRI: Participants lie on a table with a coil on their head. They press buttons in response to computer cues. Follow-up visit: participants will discuss their drinking habits. ...

NCT02639273 AUD Drug: Nalmefene Other: Placebo
MeSH: Alcoholic Intoxication

Genetic variation at the micro-opioid receptor gene locus, OPRM1, specifically the A118G polymorphism, is associated with differential subjective responses to alcohol. --- A118G ---

Further, the A118G polymorphism has been shown to moderate the effect of opioid receptor modulators on alcohol consumption. --- A118G ---

However, the role of A118G on nalmefene s effectivenes, and the neural substrates underlying nalmefene s therapeutic effect remain to be explored in humans. --- A118G ---

Objective: To evaluate the effect of nalmefene on alcohol self-infusion and neural response to alcohol cues in healthy male and female heavy drinkers, and to examine the role of the OPRM1 A118G polymorphism on this effect. --- A118G ---

Primary Outcomes

Description: functional MRI measure of brain activation.

Measure: Nalmefene-induced BOLD signal changes in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula

Time: Post-administration

Description: human laboratory alcohol consumption measure.

Measure: Nalmefene-induced changes in IV alcohol self-administration

Time: Post-administration

Secondary Outcomes

Description: functional MRI measure of brain activation.

Measure: Nalmefene-induced BOLD signal changes in neural processing of aversive stimuli during fMRI

Time: Post-adminstration

Description: human laboratory alcohol consumption measure.

Measure: Genotypic modulation (at the OPRM1 118 location) of Nalmafene's effects on primary outcome measures (BOLD signal change during alcohol reward processing and IV alcohol self-administration).

Time: Post-administration

24 Validation of a Test System for Development of Medications for Alcoholism

Using theTEMA (test system for development of medications for alcoholism) it can be shown, that naltrexone administration reduces the willingness to perform work for alcohol infusion in a laboratory experiment.

NCT02652585 Alcoholism Drug: Naltrexone Drug: Placebo
MeSH: Alcoholism

Secondary objectives: - administration of naltrexone in comparison to placebo leads to a reduction of alcohol craving and real-life drinking - administration of naltrexone in comparison to placebo leads to reduction of the CDT-Level - administration of naltrexone in comparison to placebo leads to a change in perception of subjective alcohol effects - the effectiveness of naltrexone can be predicted by the A118G polymorphism of the OPRM1 - administration of naltrexone changes the baseline and alcohol-induced ability of motor inhibition - administration of naltrexone changes the baseline and alcohol-induced regional cerebral perfusion - administration of naltrexone changes the baseline and alcohol-induced cerebral resting state activity - changes of alcohol effects to the brain activity induced by naltrexone in comparison to placebo correlate with effects of naltrexone on the willingness to work for alcohol self-administration --- A118G ---

Primary Outcomes

Description: Difference of cumulative number of work sets for alcohol in the "constant attention task" between first measurement (without medication) and second measurement (with medication)

Measure: Difference CAT Trials alcohol

Time: one year

Secondary Outcomes

Description: Difference of cumulative number of work sets for sodium chloride solution in the "constant attention task" between first measurement (without medication) and second measurement (with medication)

Measure: Difference CAT Trials sodium chloride solution

Time: one year

Description: Difference of the "break point" in the "progressive work" schedule for the work for alcohol between first measurement (without medication) and second measurement (with medication). The "break point" is the number of the last alcohol request before subjects stop to work for more alcohol.

Measure: break Point alcohol

Time: one year

Description: Maximal achieved blood alcohol concentration (BAC) in alcohol self-administration between first measurement (without medication) and second measurement (with medication)

Measure: max. BAC

Time: one year

Description: Drinking habits measured with Timeline Follow-back Interview over 45 days before study start (measured at screening) and over the entire study duration (between screening and the last day of medicinal product intake, ascertained at visit 5): drinking days, amount of alcohol per drinking day and number of days with alcohol consumption over 60 g (men) or 48 g (women)

Measure: Drinking habits

Time: one year

Description: CDT - level: (carbohydrate-deficient transferrin), measured at visit 1 and visit 5

Measure: CDT - level

Time: one year

Description: Alcohol craving in daily routine (OCD - scale) measured at visit 1 and visit 4

Measure: alcohol craving

Time: one year

Description: Difference in subjective alcohol effects between first measurement (without medication) and second measurement (with medication), measured with visual analogue scales ("Quizzer") before, during and after the alcohol infusion

Measure: subjective alcohol effects

Time: one year

Description: Capacity for motor impulse control during infusion of physiologic saline solution or alcohol as NIMPs (single-blinded), measured with the counting stroop task (in Verum and placebo group) at visit 3 and 4

Measure: motor impulse control

Time: one year

Description: Regional cerebral perfusion in ml/100 g tissue per Minute during infusion of sodium chloride solution or alcohol as NIMPs (single-blinded), measured with arterial spin labeling (ASL) under verum or placebo condition at visit 3 and 4

Measure: cerebral blood flow (CBF)

Time: one year

Description: Cerebral resting state activity during infusion of sodium chloride solution or alcohol as NIMPs (single-blinded), measured with BOLD fMRI (in Verum and placebo group) at visit 3 and 4

Measure: Cerebral resting state activity

Time: one year

Description: Medical survey concerning occurring adverse events at visit 1 to 5

Measure: adverse events

Time: one year

Description: ALAT (alanine aminotransferase) in µmol/ s*l before inclusion (screening visit), at visit 4 and after finishing all study relating interventions (visit 5)

Measure: ALAT

Time: one year

Description: ASAT (aspartate aminotransferase) in µmol/ s*l before inclusion (screening visit), at visit 4 and after finishing all study relating interventions (visit 5)

Measure: ASAT

Time: one year

Description: Gamma-GT in µmol/ s*l before inclusion (screening visit) and after finishing all study relating interventions (visit 5)

Measure: Gamma-GT

Time: one year

Description: standard blood cell count before inclusion (screening visit), at visit 4 and after finishing all study relating interventions (visit 5)

Measure: standard blood cell count

Time: one year

Description: creatinine in µmol/l before inclusion (screening visit)

Measure: creatinine

Time: one year

Description: lipase in µmol/ s*l before inclusion (screening visit) and after finishing all study relating interventions (visit 5)

Measure: lipase

Time: one year

Description: CRP (C-reactive protein) in mg / l before inclusion (screening visit) and after finishing all study relating interventions (visit 5)

Measure: CRP

Time: one year

25 A Pragmatic, Phase III, Multi-site, Double-blind, Placebo Controlled, Parallel Arm, Dose Increment Randomised Trial of Regular, Low Dose Extended Release Morphine for Chronic Refractory Breathlessness

Breathlessness is an overwhelming symptom affecting tens of thousands of Australians every day. For many people, it persists even when all the underlying causes have been optimally managed (chronic breathlessness). In these circumstances, it often occurs at rest or with minimal exertion. Evidence from a number of clinical studies suggests that a small, regular dose of morphine helps to reduce safely the sensation of breathlessness. However, it is not well established which patients derive more benefit and what is the net clinical effect of this treatment (weighing benefits and harms). This is a phase III, multi-site, randomised, double-blind, placebo-controlled trial with patients with chronic obstructive pulmonary disease (COPD) and severe chronic breathlessness which will explore several important questions: - Are regular, low doses of morphine at four possible doses over 3 weeks more effective than placebo at improving breathlessness? - Does increasing the dose in people who already are experiencing some benefit provide even greater reduction in worst breathlessness? - Does the medication have any effect on daily activity and quality of life? - What are the common or serious side effects of this intervention? - Does the benefit from the medication outweigh the side effects it produces? - Are there specific characteristics of people who are more likely to receive benefit from extended release morphine? Participants will receive once daily extended release morphine (plus laxative, docusate with senna), or placebo (placebo laxative) in addition to their usual medication for up to 3 weeks at increasing doses. Participants will have a medical interview and physical examination to collect some general health information, and baseline measurements including; daily activity, symptoms, and quality of life. A small amount of blood may be required to check eligibility. Further blood samples may be taken at week 1 and 3 to enable testing on how individuals respond to opioids, further consent will be obtained for these samples. Data on benefits, side effects, and medical care will be collected during comprehensive weekly visits. Participants will also fill out a simple diary twice daily for weeks one to three of the study, and for one day each week during an optional 6 month extension stage. The outcome of this study may enable better management of symptoms and activity in people COPD with medicines that are shown to be effective and safe.

NCT02720822 Chronic Obstructive Pulmonary Disease Dyspnea Drug: Placebo Drug: Morphine Sulfate Drug: Plus laxative (Docusate with senna) Drug: Plus placebo laxative Device: FitBit charge HR (Accelerometer)
MeSH: Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Dyspnea
HPO: Chronic obstructive pulmonary disease Dyspnea Obstructive lung disease Respiratory distress

Pharmacogenetic opioid profile - Mu receptor (A118G) polymorphism. --- A118G ---

The baseline blood samples will be analysed to detect the presence of Mu receptor (A118G) polymorphism. --- A118G ---

Primary Outcomes

Description: Rated on a 0-10 numerical rating scale (NRS). Measured at baseline, Stage1-3 (daily diary) and Stage 4 (weekly diary). The primary endpoint is: The difference between morphine sulphate 8mg and placebo (end of week1) The difference of morphine sulphate 16 mg and placebo (end of week 1)

Measure: Change from baseline worst breathlessness intensity over the previous 24 hours

Time: Week 1

Description: Difference from the baseline in the number of steps per day measured using the Fitbit(Charge HR). Measured at baseline, end of week 1, and end of week 3. The primary endpoint is: The difference between morphine sulphate 8mg and placebo (end of week 1) The difference between morphine sulphate 16mg and placebo (end of week 1) Comparison between baseline and end of week 3

Measure: Change from the baseline in the number of steps per day

Time: Week 3

Secondary Outcomes

Description: Measured at baseline and at the weekly visit for the randomisation phase, and then at the study exit in order to assess the theoretical risk of opioids worsening respiratory failure. Stages 1-4.

Measure: Change from baseline end-tidal carbon dioxide

Time: Up to week 15

Description: Measured at baseline and at the weekly visit for the randomisation phase, and then at the study exit in order to assess the theoretical risk of opioids worsening respiratory failure. Concomitant use of oxygen will be recorded. Stages 1-4.

Measure: Change from baseline pulse oximetry

Time: Up to week 15

Description: Rated on a 0-10 numerical rating scale (NRS). Measured at baseline, weeks 1-3 (daily diary) and stage 4 (weekly diary).

Measure: Change from baseline intensity of breathlessness "average"

Time: Up to week 15

Description: Rated on a 0-10 numerical rating scale (NRS). Measured at baseline, weeks 1-3 (daily diary) and stage 4 (weekly diary).

Measure: Change from baseline distress from breathlessness over the previous 24 hours

Time: Up to week 15

Description: Chronic Respiratory Questionnaire - Dyspnoea and Mastery Subscales. Baseline and end of Weeks 1-3.

Measure: Change from baseline perceived-impact of breathlessness

Time: Up to week 3

Description: Rated on the Modified Medical Research Council Breathlessness Scale (mMRC). Measured at baseline and at the conclusion of the study.

Measure: Change from baseline functional impact of breathlessness

Time: Up to week 15

Description: Measured using the Fitbit(Charge HR). Assessed at baseline (2 days), weeks 1 and 3.

Measure: Change from baseline sleep minutes

Time: Week 3

Description: Measured using the Fitbit(Charge HR). Given in number of movements per night (e.g. rolling over). Assessed at baseline (2 days), weeks 1 and 3.

Measure: Change from baseline sleep activity

Time: Week 3

Description: Measured using the Fitbit(Charge HR). Difference from baseline in the number of active minutes per day. Assessed at baseline (2 days), weeks 1 and 3.

Measure: Change from baseline in activity levels

Time: Week 3

Description: Measured using the Fitbit(Charge HR). Difference from baseline number of calories spent per day. Assessed at baseline (2 days), weeks 1 and 3.

Measure: Change from baseline total energy expenditure

Time: Week 3

Description: Measured using Australian-modified Karnofsky Performance Status (AKPS). Baseline, Stage1, Stage2, Stage3 and Stage 4.

Measure: Change from baseline performance status

Time: Up to week 15

Description: Measured using Barthel Index. Baseline and Stage 4.

Measure: Change from baseline activities of daily living

Time: Up to week 15

Description: Rated on a 4 point Likert scale. Measured at baseline, weeks 1-3 (daily diary) and stage 4 (weekly diary).

Measure: Change from baseline in sleep quality

Time: Up to week 15

Description: Thirty (30) participants at the Sydney and Adelaide sites will be invited to undertake a simple, non-invasive home sleep study using the ResMed ApneaLink Plus device. Baseline and Stage3.

Measure: Change from baseline in objective sleep testing

Time: Week 3

Description: Up to ten (10) participants will also undergo two (baseline and Stage 1) in-laboratory overnight sleep studies in Sydney and Adelaide.

Measure: Change from baseline Polysomnography

Time: Week 3

Description: Twenty (20) participants in Adelaide and Sydney. Baseline and on day 2 and 7 of the first week in an office-based simulator - AusEd.

Measure: Change from baseline Driving ability

Time: Week 3 + 2 days

Description: The baseline blood samples will be analysed to detect the presence of UGT2B7*2 and *28 polymorphisms.

Measure: Pharmacogenetic opioid profile - Number of participants with UGT2B7*2 and *28 polymorphisms

Time: Baseline (1 day)

Description: The baseline blood samples will be analysed to detect the presence of P-glycoprotein polymorphism (ABCB1 5SNPs in a haplotype block)

Measure: Pharmacogenetic opioid profile - Number of participants with P-glycoprotein polymorphism (ABCB1 5SNPs in a haplotype block)

Time: Baseline (1 day)

Description: The baseline blood samples will be analysed to detect the presence of 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572 polymorphism

Measure: Pharmacogenetic opioid profile - Number of participants with 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572 polymorphism

Time: Baseline (1 day)

Description: The baseline blood samples will be analysed to detect the presence of Mu receptor (A118G) polymorphism

Measure: Pharmacogenetic opioid profile - Mu receptor (A118G) polymorphism

Time: Baseline (1 day)

Description: In a subset of 55 participants, morphine peak plasma concentrations will be analysed (4 blood samples over 8 hours) at steady state (end of week 1).

Measure: Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine Peak Plasma Concentration [Cmax]

Time: Week 1

Description: In a subset of 55 participants, morphine AUC will be analysed (4 blood samples over 8 hours) at steady state (end of week 1).

Measure: Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine Area Under the Curve (AUC)

Time: Week 1

Description: In a subset of 55 participants, M6G Peak Plasma Concentration will be analysed (4 blood samples over 8 hours) at steady state (end of week 1).

Measure: Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-6-glucuronide (M6G) Peak Plasma Concentration [Cmax]

Time: Week 1

Description: In a subset of 55 participants, M6G AUC will be analysed (4 blood samples over 8 hours) at steady state (end of week 1).

Measure: Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-6-glucuronide (M6G) Area Under the Curve (AUC)

Time: Week 1

Description: In a subset of 55 participants, M3G Peak Plasma Concentration will be analysed (4 blood samples over 8 hours) at steady state (end of week 1).

Measure: Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-3-glucuronide (M3G) Peak Plasma Concentration [Cmax]

Time: Week 1

Description: In a subset of 55 participants, M3G AUC will be analysed (4 blood samples over 8 hours) at steady state (end of week 1).

Measure: Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-3-glucuronide (M3G) Area Under the Curve (AUC)

Time: Week 1

Description: Baseline and study completion. To explore whether longer term morphine treatment is associated with decreased levels of testosterone.

Measure: Change from baseline serum testosterone level

Time: Week 15

Description: Rated on a Lickert Scale. Baseline, weeks 1-3 (daily diary), Stage 4 (weekly diary): Includes constipation, anxiety, appetite, nausea, vomiting, drowsiness, difficulty thinking clearly, problems passing urine, itch, other symptoms.

Measure: Adverse Effects

Time: Up to 15 weeks

Description: Measured using the Edmonton Symptoms Assessment Scale (ESAS)

Measure: Change from baseline in concurrent symptoms

Time: Up to 15 weeks

Description: Rated using the Hospital Anxiety and Depression Scale (HADS). At baseline, completion of randomization stage and study exit.

Measure: Change from the baseline anxiety and depression

Time: Up to Week 15

Description: Participant-rated 7 point scale of the perception of their change, specifically their improvement since the commencement of the study. Measured at the end of Stages 1-3 and conclusion.

Measure: Change in baseline global impression of change

Time: Up to 15 weeks

Description: Measured with EQ-5D-5L questionnaire. Baseline, Stages 1-3, Stage 4, conclusion.

Measure: Change from baseline health-related quality of life

Time: Up to 15 weeks

Description: Measured with the COPD Assessment Test (CAT) Baseline, Stages 1-3, Stage 4 and conclusion.

Measure: Change from baseline health-status in COPD

Time: Week 3

Description: Asked at the end of week 1 and at the conclusion/drop-out of the study. A 3-point Likert scale will be used.

Measure: Blinded-patient preference to continue the treatment [3-point Likert Scale]

Time: Up to week 15

Description: Scored using the Zarit Burden Interview (ZBI) 12 item short-form questionnaire. Baseline, end of weeks 1-3, stage 4.

Measure: Change from baseline caregiver Impact

Time: Up to week 15

Description: From randomisation to 28 days post treatment or death (whichever is the shorter period). Estimated based on all health-care contacts including length of hospitalizations, emergency department visits, DRG codes, community health visits, GP and community nurse visits, outpatient visits and date of death. These participant level data allow within trial modeling using bootstrapping methods of replicates for costs and consequences of alternative strategies, allowing for covariance between costs and effects. Incremental net monetary benefit and cost-effectiveness acceptability curves will be estimated at potential threshold values for an additional responder.

Measure: Economic Evaluation - Cost per responder

Time: Up to week 4

Description: Evaluation using the Subjective Opioid Withdrawal Scale (SOWS) for 3 consecutive days. After the completion of the study (Weeks 1-15).

Measure: Opioid Withdrawal

Time: Up to week 15 + 3 days

26 Clinical Pharmacogenetic of Ibuprofen Enantiomers After Lower Third Molar Surgeries

The present clinical trial randomized will be to assess the link between the different haplotypes of CYP2C8 and CYP2C9 genes and the clinical efficacy of ibuprofen after lower third molar extractions. Onset, duration of postoperative analgesia, duration of anesthetic action on soft tissues, intraoperative bleeding, hemodynamic parameters, postoperative mouth opening and wound healing at the 7th postoperative day were evaluated. For this purpose, 200 healthy volunteers underwent removal of one lower third molar, under local anesthesia with articaine 4% (1:200,000 adrenaline) will be genotyped and phenotyped for these genes and their postoperative records with all data collected will be compared with the haplotypes found in the Brazilian population.

NCT03169127 Pain Other Surgical Procedures Impacted Third Molar Tooth Drug: Ibuprofen 600 mg
MeSH: Tooth, Impacted
HPO: Impacted tooth

We will evaluate also the relationship between the different haplotypes of OPRM1 gene (SNP A118G), the salivary concentrations of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10 and TNF-±), and preoperative conditioned pain modulation. --- A118G ---

Primary Outcomes

Description: Subjective evaluation of postsurgical pain, which was annotated by the volunteer after the surgery, in a Visual Analogue Scale (VAS, 0-100 mm). The subjective pain evaluations will be performed by patients at the following times after administration of the drug [0, 15, 30 and 45 min, 1; 1.5; 2; 3; 4; 5; 6; 7; 8; 10; 12; 16; 24 hr, 48, 72 and 96 h]. What will be taken into account on this outcome is the representation of the postsurgical pain, that will be noted on the Visual Analogue Scale (in millimeters) in respective moments.

Measure: Evaluation of changes in the postsurgical pain during the first 24 hours until 96 hours after the procedure

Time: Seventh postoperative day

Description: Quality of anesthesia during surgery based on a category 3point scale: 1) the patient reported no discomfort; 2) the patient reported discomfort, without the need to supplement the anesthesia; 3) reported some discomfort by the patient, requiring anesthesia complementation. Intraoral bleeding that will be evaluated by the surgeon according to a 3point scale (1: minimal, 2: normal and 3: Maximum), immediately after the following steps: injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing.

Measure: Quality of anesthesia

Time: During the surgical procedure

Description: Intraoperative bleeding, rated by the surgeon according to a 3 point category rating scale (1 minimal bleeding; 2 normal bleeding; 3 excessive bleeding) (SISK, 1986), immediately after the following steps: injection of the first cartridge of articaine, tissue incision, flap reflection, bone removal (when this procedure was necessary), tooth extraction, cleaning of the operated site, and completion of suturing.

Measure: Intraoperative bleeding during the surgeries steps

Time: During the surgical procedure

Description: Systolic blood pressure, diastolic, and mean to be verified and recorded at surgical moments previously described (injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing), carried out with the aid of a system for monitoring hemodynamic parameters.

Measure: Blood pressure variability during the surgeries steps

Time: During the surgical procedure

Description: Heart rate to be verified and recorded surgical at moments described above, carried out with the aid of a system for monitoring hemodynamic parameters.

Measure: Heart rate variability during the surgeries steps

Time: During the surgical procedure

Description: Oxygen saturation to be verified and recorded at surgical moments described above, carried out with the aid of a system for monitoring hemodynamic parameters.

Measure: Oxygen saturation variability during the surgeries steps

Time: During the surgical procedure

Description: Subjective evaluation of postsurgical pain at the moment of the rescue medication consumption which was annotated by the volunteer after the surgery, in a Visual Analogue Scale (VAS, 0-100 mm).

Measure: Subjective evaluation of postsurgical pain at the moment of the rescue medication utilization

Time: Seventh postoperative day

Secondary Outcomes

Description: Mouth opening (mm) between the mesial-incisal corners of the upper and lower right central incisors at maximum opening of the jaws was measured and recorded before the surgery and during the second and seventh postoperative days.

Measure: Postoperative mouth opening

Time: Second and Seventh postoperative days

Description: Will only be considered those surgeries in which there is no difference in the duration time of the procedure between the patients. This time count will be started after the administration of the first local anesthetic. Unit of mesure used will be hours.

Measure: Onset and duration of surgery after administration of local anesthetic

Time: During the surgery

Description: Will be considered as adverse reactions: gastrointestinal irritation, nausea, vomiting, bleeding, allergy, headache, dizziness, drowsiness or any other type of reaction presented after surgery.

Measure: Incidence, type and severity of adverse reactions after the surgery

Time: Seventh postoperative day

Description: The total amount of rescue medication that was used by the patient during the postoperative period (Acetominophen- 750 mg) will be analyzed.

Measure: Total amount of rescue medication

Time: Seventh postoperative day

Description: It will apply the method used by Ustun et al. (2003), which takes into account the sum of the following measures (obtained with flexible tape measure): A) distance between the lateral corner of the eye and the gonion, B) away from the tragus corner of the mouth and C) away from the tragus to the soft tissue of pogonion. Preoperative sum of three measures will be considered as the baseline that way. The difference between the values obtained in the postoperative period and baseline indicate the facial edema in the 2nd and 7th days.

Measure: Measurement the facial edema

Time: On the second day after surgery and on the seventh day after surgery.

27 Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse

This investigation will be the first study assessing genetic modulation of naltrexone's NTX effects upon the abuse liability of a stimulant drug (methamphetamine). The study team will assess the ability of oral NTX to block the reinforcing and positive subjective effects of intranasal (IN) methamphetamine (30mg/70kg). This investigation could identify an important Gene x Pharmacological interaction, contributing to the personalization of stimulant abuse pharmacotherapy.

NCT03226223 Substance Use Disorders Methamphetamine Abuse Drug: Intranasal Methamphetamine
MeSH: Substance-Related Disorders

Substance Use Disorders Methamphetamine Abuse Substance-Related Disorders A recent meta-analysis concluded that the OPRM1 A118G SNP (rs1799971) significantly moderates the treatment efficacy of Naltrexone (NTX) in treating alcohol abuse, increasing the treatment efficacy by over 2-fold among G-allele carriers (AG/GG). --- A118G ---

Medication effects on these validated predictors of abuse potential will be compared between A118G A allele homozygotes (AA) and G-allele carriers (AG/GG; an anticipated 25% of the total sample), in order to assess genetic moderation of treatment outcome. --- A118G ---

Primary Outcomes

Description: To assess the reinforcing effects of methamphetamine, participants complete a drug vs. money self-administration procedure. The outcome measure for this procedure is their percentage of choices for drug (methamphetamine) choices.

Measure: Percentage of methamphetamine choices.

Time: 1 day.

Secondary Outcomes

Description: Participant ratings of methamphetamine "Liking," on a 100 mm visual analog scale. Participants are asked to indicate on a 100 mm line the extent to which they agree with the description of the drug provided. The 0 mm end of the line indicates "Not at All," while the 100 mm indicates "Extremely."

Measure: Positive subjective effects of methamphetamine.

Time: 1 day

28 Safety, Efficacy, Pharmacokinetics, and Pharmacogenomics of Extended-Release Naltrexone in Pregnant Women

This is a multi-center prospective comparative cohort study examining the safety, efficacy, pharmacokinetics, and pharmacogenomics of naltrexone for pregnant women with opioid use disorder. Pregnancy, delivery, and maternal and infant outcomes to 12 months post-delivery will be examined and compared with a cohort treated with buprenorphine/naloxone.

NCT03718104 Opioid-use Disorder Neonatal Abstinence Syndrome Pregnancy, High Risk Alcohol Use Disorder Other: Pharmacokinetic analysis Other: Safety and Efficacy Genetic: Genetic and epigenetic analysis Other: Breast milk analysis
MeSH: Neonatal Abstinence Syndrome Disease Alcoholism

Mothers will be genotyped for the ORPM1 A118G SNP at 36 weeks gestation from a blood sample to see if genotype is associated with treatment response and risk for relapse.. Maternal saliva OPRM1 methylation status. --- A118G ---

Primary Outcomes

Description: Maternal relapse of illicit and/or unprescribed drug use from maternal/provider report and or from urine toxicology testing at any point during the pregnancy and up to 12 months after delivery

Measure: Maternal drug use relapse

Time: up to 12 months post-delivery

Secondary Outcomes

Description: Number and type of side effects or adverse events such as injection site reactions, gastrointestinal upset, syncope, headaches, or dizziness reported by participant or provider

Measure: Naltrexone side effects or adverse events

Time: up to 12 months post-delivery

Description: Mean fetal heart rate (FHR), FHR variability, and episodic accelerations of FHR (count) from each routine care non-stress test (NST) in the third trimesters.

Measure: Fetal heart rate monitoring from NST

Time: 27- 41 weeks gestation

Description: The biophysical profile uses electronic fetal heart rate monitoring to examine the fetus. There are five components measured during the biophysical examination (fetal breathing movements, gross body movement, fetal tone, amninotic fluid volume and whether the NST is reactive or nonreactive. A score of 2 points is given for each component The points are then added for a possible maximum score of 10. The test is continued until all criteria are met or 30 minutes have elapsed. HIgher scores are more favorable.

Measure: Biophysical profile score calculated from NST

Time: 27 - 41 weeks gestation

Description: Hair cortisol levels will be obtained from maternal hair samples obtained at birth and 4 weeks after delivery, and compared between the naltrexone and buprenorphine groups. Higher hair cortisol levels in the mother may indicate exposure to higher levels of stress over the preceding 3 months period.

Measure: Maternal hair cortisol levels

Time: Birth and 4 weeks post-delivery

Description: Hair cortisol levels will be obtained from infant hair samples obtained at birth and 4 weeks after delivery, and compared between the naltrexone and buprenorphine groups. Higher hair cortisol levels in the infant may indicate exposure to higher levels of stress over the preceding 3 months period.

Measure: Infant hair cortisol levels

Time: Birth and 4 weeks post-delivery

Description: Fetal growth will be assessed at the time of routine growth scans at 18-20, and then q4 weeks until delivery. Fetal size will be compared to Intergrowth standards to produce z-scores and SGA (<10%ile) for averaged 2nd and 3rd trimester measurements.

Measure: Fetal growth based on ultrasound measurements

Time: 18 - 41 weeks gestation

Description: Fetal, placental, or amniotic fluid anomalies identified during routine ultrasounds in the second and third trimesters will be documented.

Measure: Congenital fetal anomalies by ultrasound

Time: 18 - 41 weeks gestation

Description: Infants will be routinely assessed at birth during the physical examination for any external anomalies.

Measure: Congenital anomalies by physical examination

Time: Birth

Description: NAS diagnosis will be based on opioid withdrawal signs and symptoms in the infant after delivery as assessed by NAS withdrawal scores (either the Finnegan score or the via the ESC (Eat, Sleep, Console) assessment tool. The Finnegan scale assesses 21 of the most common signs of neonatal drug withdrawal syndrome and is scored on the basis of pathological significance and severity of the adverse symptoms, which sometimes requires pharmacological treatment. Measurements are performed every 4 hours, typically with 2-3 consecutive scores that are equal to or greater than 8, or 1-2 scores of 12 or greater, pharmacologic treatment for withdrawal is started. For the ESC assessment, clinicians assess whether or not the infant has poor feeding, is unable to sleep for at least 1 hour after feeding, and is consolable (rating of 1-3) due to symptoms of opioid withdrawal. Poor feeding, sleeping, or consolability triggers a huddle and possible start of pharmacologic treatment.

Measure: Diagnosis of Neonatal Abstinence Syndrome (NAS)

Time: From birth to 30 days

Description: The need for pharmacologic treatment will be recorded as Y/N as will the need for adjunctive agents.

Measure: Infant need for pharmacologic treatment

Time: From birth to 30 days

Description: The need for adjunctive agents will be recorded as Y/N

Measure: Infant need for adjunctive agent

Time: From birth to 30 days

Description: The total mgs of morphine/methadone needed for pharmacologic treatment and the total number of total opioid treatment days will be obtained from the birth hospitalization medical records.

Measure: Infant opioid replacement pharmacologic treatment

Time: From birth to 30 days

Description: Number of continuous days infant hospitalized after birth.

Measure: Infant birth hospitalization length of stay

Time: From birth to 30 days

Description: Growth parameters of infant weight in grams will be obtained by the clinician at birth, 4 weeks, and 12 months at each study visit. Percentiles will be calculated.

Measure: Infant weight

Time: Birth, 4 weeks, and 12 months

Description: Growth parameters of infant length measured by the clinician in cm will be obtained at birth, 4 weeks, and 12 months at each study visit. Percentiles will be calculated.

Measure: Infant length

Time: Birth, 4 weeks, and 12 months

Description: Growth parameters of infant head circumference in cm will be obtained by the clinician at birth, 4 weeks, and 12 months at each study visit. Percentiles will be calculated.

Measure: Infant head circumference

Time: Birth, 4 weeks, and 12 months

Description: The NICU Network Neurobehavioral Scale (NNNS) is a comprehensive assessment of both neurologic integrity and behavioral functioning, including signs of stress. It assesses the full range of infant neurobehavioral performance (orientation to auditory and visual stimuli); infant stress (color changes, tremors, startles), neurologic functioning (reflexes, tone); some features of gestational age; self-soothing capacities; states and their organization. The 13 summary scores (i.e., orientation, habituation, hypertonicity, hypotonicity, excitability, arousal, lethargy, non-optimal reflexes, asymmetric reflexes, stress, self-regulation, quality of movement, handling) are typically used to summarize a clinical examination .

Measure: Infant neurobehavior-function assessed by the NNNS

Time: 4 weeks of age

Description: The Bayley III is a standard series of measurements used to assess the development of infants and toddlers, ages 1-42 months. It has 5 scales, 3 administered with child interaction - cognitive, motor, language, and 2 with parent questionnaires- social-emotional, adaptive behavior. A developmental quotient (DQ) is derived from the results.

Measure: Infant neurodevelopment assessed by Bayley III

Time: 12 months of age

Description: Naltrexone levels from maternal blood and plasma will be obtained at regular intervals for pharmacokinetic analysis.

Measure: Pharmacokinetic analysis of maternal naltrexone levels

Time: 2nd trimester, 3rd trimester, delivery, 2-4 days after delivery, 4 weeks post-delivery

Description: Naltrexone levels from infant blood and plasma will be obtained at regular intervals for pharmacokinetic analysis.

Measure: Pharmacokinetic analysis of infant naltrexone levels

Time: Delivery, 2-4 days after delivery, 4 weeks post-delivery

Other Outcomes

Description: Mothers will have a genome wide methylation profile at 36 weeks gestation from a blood sample.

Measure: Maternal DNA methylation profile

Time: 36 weeks gestation

Description: Mothers will be genotyped for the ORPM1 A118G SNP at 36 weeks gestation from a blood sample to see if genotype is associated with treatment response and risk for relapse.

Measure: Mu opioid receptor (OPRM1) gene single nucleotide (SNP) genotype

Time: 36 weeks gestation

Description: Mothers will have their OPRM1 methylation status examined via saliva samples to see if OPRM1 methylation is altered by maternal treatment.

Measure: Maternal saliva OPRM1 methylation status

Time: Birth, 4 weeks postpartum

Description: Infants will have their OPRM1 methylation status examined via saliva samples at to see if OPRM1 methylation is altered by maternal treatment.

Measure: Infant saliva OPRM1 methylation status

Time: Birth, 4 weeks postpartum

Description: Naltrexone levels will be measured from the breast milk of breastfeeding mothers who are on naltrexone.

Measure: Breast milk naltrexone level

Time: 4 weeks postpartum

Description: Length of time mother continues medication assisted treatment (MAT) from provider or participant report

Measure: Retention in addiction treatment

Time: up to 12 months post-delivery

Description: Data on maternal healthcare utilization, including emergency room visits, primary care visits, and re-hospitalizations will be collected.

Measure: Maternal healthcare utilization

Time: up to 12 months post-delivery

Description: Data on infant healthcare utilization, including emergency room visits, primary care visits, and re-hospitalizations will be collected.

Measure: Infant healthcare utilization

Time: up to 12 months post-delivery


HPO Nodes


Obstructive lung disease
Genes 84
HLA-DPA1 DNAH9 CCDC103 PTPN22 DNAH11 DNAAF3 HIRA LRRC56 CYBB GLA LRRC6 GAS8 SERPINA1 CFAP298 SPAG1 CCDC40 ARMC4 CYBA GAS2L2 CCDC151 NCF1 NFKB1 MYH7 DNAAF2 RREB1 MMP1 CFAP221 WIPF1 HLA-DPB1 DNAAF1 RSPH4A APC OFD1 NME8 DNAAF4 SCNN1B DNAI2 CFTR CCDC65 TBX1 GP1BB HMOX1 DNAAF4 ARVCF CFAP300 SCNN1A DNASE1L3 SEC24C FOXJ1 DNAI1 DNAAF6 NCF4 SCNN1G CCNO DNAH5 GLA CCDC114 SERPINA1 RSPH1 CCDC39 STK36 JMJD1C CTLA4 DNAJB13 RPGR MGP PRTN3 TTC25 DNAL1 DNAH1 ZMYND10 RSPH3 TBX1 COMT RSPH9 UFD1 SPEF2 NCF2 DNAAF5 DRC1 WAS CYBC1 MCIDAS HYDIN
Respiratory distress
Genes 230
DNAH9 DNAH11 ND5 EPHB4 SBDS TBC1D24 SPAG1 ORC1 TRNW ZFPM2 ND6 DNAAF3 GAS2L2 CCDC151 LYRM4 DISC1 CHRNE TRNV STT3B NDUFAF3 IFT81 CDT1 ETFA TRMU RSPH4A GBA TACO1 SLC52A3 NME8 COL2A1 COLQ FBP1 DNAAF4 ALDH7A1 MYO9A AGRN CCDC65 SLC18A3 TRNN FGFR2 ORC1 CFAP300 RUNX2 DNAI1 TRAK1 COX6B1 RSPH1 CCDC39 PMM2 ORC4 SLC2A10 DMPK DNAL1 MAPT ND2 ZMYND10 KAT6A NKX2-1 SURF1 COX8A MMAB SLC35A1 NUP214 GBA GAS8 CFAP298 DPM1 FGFR1 PUF60 IFT52 EP300 TRNE COX14 DNAAF2 MPC1 COL2A1 GMNN BMPER NDUFS2 ORC6 NAGS DNAAF1 PRSS1 PET100 SRP54 HLCS FAM20C COX20 EOMES CSF2RA RPS28 AIMP2 AIFM1 HCCS DNAAF6 STT3B DNAH5 SETBP1 PRRX1 SFTPC OTX2 SLC25A3 TTC25 LAMB2 SLC5A7 SPEF2 DNAAF5 TRIP11 LIFR TUBB4A NAGS ACADVL TK2 LGI4 ARMC4 COA8 SNAP25 ND3 RPS26 SERPING1 COL2A1 EFTUD2 ADCY6 KCNA1 FOXP3 CFAP221 IL1RN ND4 TRIP11 NGLY1 STAT5B MAPT COPA GATA6 MMAA MMUT ABCA3 SFTPB XYLT1 GATA6 VPS33A FOXJ1 CSF2RB MEGF10 SDCCAG8 ADAMTS13 ZIC3 CHAT FASTKD2 ETFB CCNO NDUFB8 CHAT STK36 FGFR2 TRNS1 KLHL7 POMT1 TRNE CNTNAP1 DNAH1 RSPH3 RSPH9 GNAI3 FBLN5 TRNL1 PRRX1 EDN1 DRC1 VAMP1 ADNP COX7B CPT2 CCDC103 ND1 DNAAF3 LRRC56 LRRC6 CCDC40 SLC25A1 SLC12A3 CFTR COQ7 SCO2 EDA SCO2 DMPK FOXF1 EFEMP2 PLCB4 UBE3B NKX2-1 OFD1 TRNK COL13A1 ITGA3 ETFDH COL2A1 DNAI2 SOX9 DNAJC21 SCO1 SYT2 USP9X DPM2 FGFR2 SSR4 USP9X COX10 CDC6 NDUFB11 CCDC114 FGFR2 DYNC2LI1 TRPV6 CDC45 DNAJB13 RPGR ATP6 CREBBP CLCNKB SIK1 CTRC DPM2 MMUT BMPER SPINK1 ERF MCIDAS HYDIN
Addictive behavior
Genes 17
RARA IRF2BP2 ZBTB16 HTR2A NPM1 NABP1 PML ADH1B BCOR PRKAR1A TBL1XR1 STAT3 STAT5B GABRA2 FIP1L1 NUMA1 ADH1C
Chronic obstructive pulmonary disease
Genes 31
HLA-DPA1 TBX1 GP1BB HMOX1 PTPN22 DNAAF4 HIRA CYBB SERPINA1 ARVCF CYBA SEC24C NCF1 NFKB1 MYH7 NCF4 GLA SERPINA1 JMJD1C CTLA4 RREB1 MMP1 WIPF1 PRTN3 HLA-DPB1 TBX1 COMT UFD1 NCF2 WAS CYBC1
Abnormal lung morphology
Genes 1201
GPC3 ARID1B NFKBIA POLR3H TNFRSF11A GLI3 CLPB BIRC3 IL17RA ZFPM2 WDR34 CTSC BTK FCGR3A PORCN STRA6 PIGL FRAS1 PHGDH SLC18A3 STAT3 TERT CFTR TAF1 GLI1 CFTR PRKCD DNAAF4 EGFR TGFB1 LEPR SLC18A3 ZMPSTE24 COL2A1 DICER1 PEPD DLL3 NGLY1 TERC WAS MARS1 TTC21B DNAAF2 SELENON IRAK4 SFTPA2 ARMC4 FBN1 GBA RSPH1 DYNC2LI1 SLC2A10 ALOX12B DNAL1 TINF2 UNG DHCR24 ADAMTS2 IL2RB NKX2-1 HOXD13 SFTPB KIAA0586 SPINK5 HIRA GBA GAS8 CEP57 CFAP298 WDR60 GNPTAB KRAS LEP MCTP2 KAT6B PUF60 CD3G FCN3 CYBA TBL1XR1 DOK7 CHRND SMN1 EP300 BUB1B DOCK8 EFEMP2 ESS2 SMPD1 SCNN1G CSF2RA RBPJ BCOR HLA-DPB1 KAT6B DNAAF1 ICOS KIF11 MEFV SPAG1 CCDC40 TRAIP CARD11 RSPH4A IL10 LZTR1 CHRNG PTPRC NOTCH3 SNORD115-1 NOTCH3 ARVCF BACH2 RLIM RAG2 ITCH DGCR6 MST1 FCGR2A TBX5 CD28 IDUA SLC25A22 STN1 MGP CD8A SULT2B1 CHST14 JMJD1C TPM2 CCDC103 HELLS FCGR2A MRPS22 SLC5A7 CEP55 SDR9C7 HERC2 GPC6 TGFBR1 STAT3 TTC37 CD247 MESP2 GTF2I CDC45 BLNK IGH CCNQ KIAA0586 BLNK FOXP1 MAT2A SMARCA4 SGCG FAM20C PRKN MPLKIP NPAP1 FOXE3 NCF1 SMAD4 CYP4F22 TPP2 RNU4ATAC EIF2AK4 STAT6 NGLY1 LRBA DNMT3B CCR6 GATA6 P4HTM TRPS1 COL13A1 MIF C1R DNAAF5 SFTPB CD81 CARMIL2 GATA6 CCNQ TAP1 FGFR3 SFTPC MESP2 SMAD4 SNX10 DOCK8 SHROOM4 WDR35 GRIP1 ETFB MARS1 FLNB LETM1 TERT APOE SMPD1 CSF2RB CTLA4 SCN10A GREB1L ITGA8 NPM1 LGI4 MYH3 CR2 ARID1B SERPINF2 NHLRC2 GPC4 COL1A1 DCLRE1C NDN SGSH LRRC56 LRRC6 HPS4 BTNL2 CCDC40 ALG9 TMEM94 BTK DGCR8 CCBE1 EWSR1 WDR60 PGM3 COG4 PSAP HES7 SCN9A CFB KIAA0319L LMNA HLA-DRB1 RBM10 EFEMP2 MRAS SMARCC2 AGGF1 COL6A2 POLR3A GTF2E2 SMAD3 ALDH18A1 WRAP53 INVS ITGA3 CFI HLA-B FBLN5 DNAI2 MINPP1 FAS SLC26A2 ZAP70 DCTN4 NR5A1 CD79B NEK9 FREM2 ARHGAP31 KIF1A AFF4 BTNL2 CYP2A6 DONSON WDR34 GLA TIRAP STAT3 CCDC114 ACVRL1 PTEN DLL4 ZBTB16 GATA6 HYLS1 PIK3R1 HACD1 DPM2 KITLG RMRP DNAH11 STAT5B ERF EPM2A HYDIN G6PC3 ATM COL5A2 SNORD116-1 DNAH11 NFKB2 EPG5 BCL10 CCR1 SON ERCC2 AK2 RASA2 STRA6 SLC35A1 MS4A1 DNAAF3 REN MYH3 CCDC151 LIG4 MKKS ATP11A FBLN5 ATP6V0A2 BMPR2 SLC22A18 SOS1 RFC2 PPP2R1B TGFBR2 IFT81 WIPF1 GATA4 LFNG RAF1 NOP10 RFXANK RSPH4A HLA-B SLC52A3 NHP2 CXCR4 GSN PCNT TNFRSF13B LEP TERC CORO1A CCDC65 PTPN22 CD55 TGFBR1 IL17F ALG12 STAT4 COL11A2 MEFV NHLRC1 ABCA12 LTBP3 SCNN1B DVL3 HLA-DRB1 RPL10 NSD2 RARB TECPR2 CCBE1 EPG5 VANGL1 FLNA CCDC39 RFXANK BMPR2 CARD11 SFTPC CFH OFD1 ITCH MYH11 JAGN1 PRKAR1A LRRC6 NAA10 ITPR1 CFTR GLE1 PLP1 GPR35 INTU STAT1 NR2F2 CYBC1 ABL1 SLC35A1 HLA-DPA1 LBR PSMC3IP BRAF CASP10 RAG2 TERT CACNA1C HLA-DRB1 PHGDH CHRNA1 TRIP13 MYD88 IDUA B3GLCT NOTCH2 TAPT1 KIAA0556 AICDA CLCN7 PANK2 PAX6 MKS1 RANBP2 FARSB FGF20 FLNA ELN CIITA RSPH3 ADA DNAAF2 PLVAP BCL2 EMG1 KMT2D ZNF341 TNFRSF1A IL7R LEPR NAGLU RAG2 MESP2 CD46 WT1 ELN SCNN1A PERP HLA-DRB1 DIS3L2 DLL3 MITF CSF2RA LAMTOR2 BRAF RAG1 BLM CCR6 NSMCE3 UMPS INHBA ELN IL23R RFX5 GRHL3 IL6 LIPN WT1 TTC25 FGFR3 ADA LMNA TTC25 ACTA1 TP53 ZAP70 LOX UFD1 ALPL IGHM SCNN1G STAT3 COL3A1 RAG2 NBN FLCN LIFR TGM1 PIK3CA CACNA1B ATP5F1A GPKOW ARMC4 TREX1 NCF1 SNAP25 SERPINH1 IPW FADD CXCR4 TSC2 CD3E BUB1 MCM4 CFAP221 ERAP1 CTC1 DNAI2 KCNJ6 COPA NOTCH1 SPINK1 CCDC114 DOCK6 PLG ABCA3 SLC25A24 SOX10 LRRC8A FAS ICOS POLA1 VPS33A PRKAR1A FCGR2B CHAT PAX3 CCNO ALMS1 NCF2 ITGA8 GLB1 CHRM3 TNFRSF13C ERCC3 EVC FADD CTLA4 CD79A BMP15 H19 RSPH9 NEK8 CFTR NCF2 FLNB FASLG MAP3K8 RIT1 MECP2 TERC KLHL40 CCND1 HLA-DRB1 IKBKB DNAAF3 TP53 MAGEL2 CCN2 ACP5 CHAMP1 HYDIN TINF2 EOGT MTHFD1 SMARCB1 ABCA3 RAG1 PIK3R1 TERT PWAR1 SCARB2 OCRL MS4A1 DNAAF6 PIK3R1 CCDC39 UBE2A NKX2-1 TCF4 ACTA2 ARID2 ZBTB24 UBAC2 FRAS1 TINF2 ETFDH WDR19 GNPTAB C4A NFIX RAG2 PTEN SCNN1A RFXAP USP9X NFKB1 NIPAL4 WRN IL2RG POLE MEFV KLHL41 PKHD1 AGT TGFBR2 INPPL1 GBA MYBPC3 GUSB CITED2 CTRC CSPP1 RHOH MCIDAS DCLRE1C TIMM8A DNAH9 PEX1 SIK1 GTF2H5 IER3IP1 GUSB EPHB4 COL2A1 TBC1D24 SPAG1 MSN GAS2L2 NIPBL NFKB1 CRELD1 BRCA2 IGLL1 RNF168 ZBTB24 RFX5 TERT MKRN3 RASGRP1 PLEC NOP10 BICC1 NSDHL MUSK ENG MBTPS2 DHCR7 IRAK4 COLQ TCTN3 MYO9A TBX1 DRC1 CC2D2A IRF2BP2 WNT4 HSPG2 TAP2 KEAP1 LAMA2 DICER1 WT1 CFAP300 RIPK4 DNAI1 TBCD RRAS2 IL2RG RELA SOX4 MFAP5 IFNGR1 NOD2 GLI3 TRPV3 ZMYND10 NRAS RFXAP FOXF1 DGCR2 RSPH9 PLOD1 SLC11A1 SLC7A7 SCNN1B PKD1L1 TRIM28 SLCO2A1 CLCA4 MLXIPL CLIP2 BMP2 CCDC65 DHCR24 POU6F2 SFTPA1 FIP1L1 SERPINA1 TRIP4 USB1 UBB FLCN LAMTOR2 TBC1D24 NECTIN1 SAMD9 CCNO AARS2 LMOD3 GLDN CIITA MUC5B LCK NPM1 MMP21 IFT172 COL5A1 TBL2 ASAH1 ALMS1 DNASE1 RUNX2 DNAAF4 SH3KBP1 NPHP3 CSPP1 DNAI1 IL12A-AS1 NABP1 TSC1 TNFRSF13C SEC24C TGFB2 IDUA IL2RG CCND1 DNAAF6 MYH7 GALNS NUMA1 FUCA1 RIPPLY2 B2M SFTPC FLI1 CD3E ELANE ASCC1 TCF3 SLC29A3 RELB ERCC6 ACTA1 FGFR1 LAMB2 COMT SPEF2 AGA ELN PYROXD1 CLEC7A NAA10 KRAS GPC3 SMPD1 SOX11 REST DDR2 BCL11B SLC7A7 NUP88 FLCN EDARADD SPECC1L FAM111B MYSM1 ARID1A GNS CD79B LYST PDGFRA SRP54 PIEZO2 BGN IL1RN GATA4 TRIP11 GBA SLC26A2 NUP107 NAA10 THOC2 SELENON RARB STX1A RTEL1 TNFRSF13B GP1BB SKIV2L VPS13A BCOR BCOR INPPL1 CAV1 AP3B1 EDNRB NOTCH2 GATA2 IRF5 CSF2RB TTC7A SDCCAG8 FANCB JAK3 TBCE RTEL1 OSTM1 VHL CCDC151 NEK1 IL21 SPP1 DNAJB13 JAK3 RNF125 INSR STK36 IL7R POLA1 CD19 FOXC2 CD3D RSPH3 TRIM28 FBLN5 SNAI2 TAPBP RAPSN CYBB CCN2 DRC1 VAMP1 ADNP WT1 PTPN22 IFT80 PTPN11 ARSB SP110 ZEB2 SLC25A1 ASAH1 PCGF2 SOS2 COQ7 COL6A1 GATA6 SLC46A1 EVC2 RRAS IKBKB LPIN2 TGFB2 GLE1 GAS2L2 RREB1 TGFB1 PEPD RNU4ATAC STK11 MYL2 SCN11A C1QA ERBB2 TSC2 KLRC4 PSAT1 MYT1 DICER1 SCNN1B BTK CCDC22 DSP CFTR RYR1 ADAMTS3 CD81 WDR60 PLG SYT2 USP9X DKC1 GLI3 LMNA PRPS1 ELANE C11ORF95 WNT3 ALB RSPO2 IFT80 NME8 ATP6V1E1 TNFRSF13C RPS15A MAP3K20 DYNC2H1 TNFSF12 KAT6B ADA SMARCE1 FASLG DSG1 ELN RPGR IFT43 CREBBP PRTN3 COL3A1 LTBP4 NFE2L2 FLNA BMPER RIT1 RCBTB1 GAS8 FBN1 DPF2 BAZ1B CASP8 EHMT1 KRAS LACC1 ARHGAP31 PRSS2 CRELD1 NFKB2 WDR35 ZMYND10 IL17RA TARS1 NXN FANCB COL6A3 TCIRG1 WASHC5 CHRNG ETFA GDF1 DPP9 NME8 IL17RC AGRN CHRNG CDT1 RPGR TBX1 CBL NADK2 GTF2IRD1 PML IRF1 ABCA12 LAT IFT140 PTPN11 MANBA PARN GFI1 NBN RARA RNF113A HELLPAR PMM2 SPIDR SCNN1A ICOS TNFSF12 PWRN1 MGP USB1 TYK2 IL21R FMO3 AGA IRF5 FSHR MYRF SLC34A2 RIPK1 DNAAF1 HPGD ORC6 HPS6 NPHP3 GMNN RB1 RYR1 CFAP298 JAG1 TNFRSF13B KDM6A TSC1 SAMD9L GDF1 ROR2 WNT4 ACE TPM3 WDR34 FBN1 GBA CFI BUB3 COG4 PPP1CB TSC2 PRKG1 MYLK MUSK IGHM TSC1 TRAF3IP2 RAF1 CEP120 PGM3 IL12A TNFRSF1B DNASE1L3 EGFR ELP1 ELN FLCN PNP DNAH5 HGSNAT SETBP1 ECM1 PIGN CR2 MASP2 RTEL1 SFTPA2 AP3D1 MBTPS2 RAC1 CRTAP PIGN KAT6B IFIH1 DNAAF5 BRAF ADGRG6 FAT4 SNRPN DYNC2H1 SOX18 CD19 ACADVL TNFSF11 CYBB PTPN22 PEX13 TRIP13 TK2 AKT1 SLC2A10 GAA PRKDC ALOXE3 CR2 CYBA FUZ RAG1 PTH1R MUC5B CDCA7 LMNA TERC RAG1 CD19 CD79A DNAH5 TFRC PIEZO1 FOXP3 IRF8 NEB LYST EXOSC9 A2ML1 CD3D CRKL RYR1 NKX2-5 BAP1 TGFB3 PDGFRB DCLRE1C PARN CTLA4 CEP120 PRKAG2 DCLRE1C SLC26A2 TGFB1 CTLA4 XIAP RSPO2 IL7R TRPV4 BCL6 IKBKG FOXJ1 NELFA ZMPSTE24 IL2RG CASP8 TMEM260 RAG1 IGLL1 CFAP410 CAV1 HPS1 SERPINA1 FOXE1 UNC119 RSPH1 LIMK1 MYOD1 DYNC2LI1 RAG1 SLC26A2 PARN TRIP4 STAT1 DNAH1 FAS WDR19 DHCR7 WAS CCDC103 IL2RA TLR4 SLC12A6 ACTA1 ATM RET LRRC56 RAB3GAP2 PIGN FGF20 STAT4 IKZF1 PRKCD SLC35C1 HFE MKRN3-AS1 SH2D1A HABP2 NAB2 NCF4 XIAP MAPK1 FSHR CHD7 IGH AGTR1 WNT3 BLM HLA-DRB1 SMARCD2 NKX2-5 TBX6 STING1 ELP1 OFD1 COL13A1 NHP2 RAB27A MYO5A DKC1 FAM13A COL11A2 TRIP11 HRAS IRAK1 PRSS1 GRIP1 PLCG2 NCF4 ZNHIT3 MALT1 SCNN1G BCR NRAS TCIRG1 MEFV SOX18 TBC1D23 CEP57 SERPINF2 DNAJB13 PIK3CD FAT4 TBX1 ITGA7 RNF168 SMN1 TERT DNMT3B SMAD3 NFKB2
Allergy
Genes 21
CHD1 TGM5 ADA PLA2G7 MTOR FOXP3 PGM3 CARMIL2 SIK3 CCDC28B BBS1 NRXN1 IL4R COX4I2 MS4A2 PLCG2 SPINK5 CSTA CNTNAP2 RBM8A PGM3
Back pain
Genes 48
EMD HGD LMNA DLL3 PDGFB ATP7B CLCN7 VANGL1 TP53 TMEM43 SEC63 PLEKHM1 SMAD4 CAPN3 SYNE1 MESP2 BRCA2 SMARCB1 ALDH18A1 SUFU PRKCSH FHL1 PALB2 LMNA LRP5 LMX1B NAB2 TCIRG1 PALLD FHL1 NF2 HELLPAR SPAST SYNE2 VCP CFI TBX6 HLA-B BRCA1 STAT6 CFH PRKCSH HTRA1 FLI1 CD46 CDKN2A KRAS VCP
Low back pain
Genes 6
HTRA1 SPAST ALDH18A1 NAB2 TBX6 STAT6
Hypertension
Genes 410
GPC3 MPL PRKAR1A ABCG8 ND1 CYP11B1 TRNS1 B2M MMP2 BRCA2 SDCCAG8 HMBS LYZ PKD1 C8ORF37 BSCL2 WT1 SCNN1B SLC25A11 COX2 CEP19 TRNQ YY1AP1 ECE1 WT1 KCNJ5 ENPP1 FN1 PDE11A HGD SLC25A11 HSD11B2 MFAP5 GUCY1A1 DYRK1B SPRY2 SLC2A10 SMAD6 COX3 SCNN1G SCNN1B LARS2 FOXF1 NPHP4 TRNL1 TMEM67 IL12B HIRA TRIM28 MLXIPL CDH23 CLIP2 HLA-B TRNF POU6F2 NFU1 SDHC CEP290 ENPP1 EDA CYTB SDCCAG8 HLA-DPB1 SCNN1A NKX2-5 COL5A1 LEMD3 YY1AP1 TBL2 ALMS1 NOTCH3 CLCN2 ARVCF SEC24C CFH FH TGFB2 TMEM127 ARMC5 AIP SDHA JMJD1C COX1 ND5 COMT NF1 CACNA1D TGFBR1 REST LDLRAP1 GTF2I PDE3A TNFRSF11B MAT2A HSD11B2 TRNH CORIN SERPINA6 BBS10 AIP MAFB FOXE3 SCN2B SMAD4 CYP11B1 TRNK SLC52A3 TRNL1 CYP17A1 GBA SDHB BBS1 HBB CCR6 XPNPEP3 ERCC4 VHL BBS7 GP1BB TRNE OSGEP PPARG NOS3 TRPC6 HMBS JAK2 VHL KRT18 TRNS1 WT1 NPHP1 SDHD INVS KCTD1 OFD1 USP8 FIG4 TRIM28 LRIG2 PCSK9 SDHB SCNN1G CCN2 COL1A1 TRNL1 WT1 PTPN22 LDLR PRKAR1A COX1 VHL TRNC COQ7 LEMD3 PRKACA MKKS BBS5 SLC52A2 SDHD TRNW COX3 RREB1 GPR101 SMAD3 INVS KIF1B DNAJB11 COX2 APOA1 RET ARHGAP31 KCNJ5 WT1 ND5 GDNF CUL3 GLA FLT1 ACVRL1 TNFRSF11A VHL GNAS PRTN3 COL3A1 ABCC6 XYLT1 CYP11B1 ADAMTSL4 FGA C3 COL5A2 BBS9 ERCC6 KCNJ5 FBN1 APOB BAZ1B PAM16 POU3F4 TMEM70 ND4 STOX1 GNAS RFC2 TGFBR2 CALR IQCB1 CYP21A2 MMP14 SLC37A4 ALX4 TRNQ TBX1 THPO GTF2IRD1 GATA5 ND6 FN1 RPGRIP1L CFB ANGPTL6 RET XYLT2 VANGL1 NR3C1 PDE11A NR3C2 POR TRNK BMPR2 MGP TRNV SUGCT RET MYH11 PRKAR1A MDH2 FMO3 KLHL3 WNK4 TMEM237 LZTFL1 TRNK IRF5 STAT1 NSMCE2 MUC1 COL4A4 HLA-DPA1 GLA IDUA NOTCH2 TRNW CC2D2A SCNN1A NR3C1 CPOX USP8 BBS2 ELN CYP11B2 SMARCAL1 LMX1B BNC2 TRIM32 MAX MKS1 PKD2 LRP6 PRKACA COL3A1 SDHD NPHP1 MAX PRKG1 MYLK HLA-DRB1 DIS3L2 CFI LMX1B ACAT1 ELN EGFR ND6 ELP1 ELN SLC37A4 PPARG CEP164 LMNA PLIN1 DLST TP53 TRNF SMAD4 LOX UFD1 FMR1 SDHB NOTCH1 SMAD4 BBS12 IFT172 ABCG5 MYMK CFHR1 TRIP13 SLC2A10 GJA1 WDPCP FUZ CYP17A1 TRNS2 WDR35 MYH7 SDHAF2 LMNA NPHP3 GUCY1A1 EXT2 HPSE2 OFD1 LMNA FGFR2 MEF2A PLIN1 COL4A3 CEP290 ACTA2 KIF1B CD2AP TGFB3 FBN1 TRNS2 SH2B3 COL4A5 NOD2 SDHC PDE3A G6PC THBD FBN1 CAV1 TTC8 ALMS1 ITGA8 LMNA GANAB LIMK1 BBIP1 CTLA4 BANF1 CCDC28B CFHR3 FBN1 H19 CACNA1H ARMC5 AIP CCND1 ADA2 ARL6 EDA2R CBS SH2B3 TET2 CACNA1D ADA2 ND1 VAC14 IFT27 PDE8B CYP11B1 TRAF3IP1 CDH23 BBS1 TMEM127 COL4A3 GNAS ELP1 ACTA2 NPHP1 MTTP WNK1 WDR19 ZMPSTE24 CD46 GCH1 KCTD1 ADA2 ABCB6 ACTN4 NFIX ENG TGFBR3 ABCC6 WRN LMNA BBS4 PKHD1 FGFR2 MC4R ERCC8 KIF1B KRT8 TBX1 JAK2 PHF21A MLX ABCC6
Impacted tooth
Genes 3
FLNA CDH11 HOXD13