SNPMiner Trials by Shray Alag


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Report for SNP rs776746

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 3 clinical trials

Clinical Trials


1 Pharmacokinetics of Clindamycin and Trimethoprim-sulfamethoxazole in Infants and Children Using PBPK

Developmental changes in physiology during childhood influence drug dosing. Failure to account for these changes leads to improper dosing, which is associated with decreased drug efficacy and safety in children. Population physiologically-based pharmacokinetic (PBPK) modeling offers the opportunity to predict optimal drug dosing based on physiologic parameters adjusted for developmental changes. PBPK models are mathematical constructs that incorporate physiologic processes with drug characteristics and genetic variances to characterize the dose-exposure relationship across the age continuum. These models integrate drug-specific (e.g., metabolism, protein binding) and systems-specific (e.g., organ size, blood flow) information to predict the effect of different factors (e.g., age, genetic variants, disease) on drug exposure. By accounting for these factors and using data from clinical trials to confirm the modeling, PBPK models can reduce the number of children needed for clinical trials while maximizing dose-based efficacy and safety. This trial will evaluate a platform to prospectively validate population PBPK models in children. The study drugs, clindamycin and Bactrim (aka TMP-SMX), are ideal candidates to evaluate population PBPK models in children due to their differing physico-chemical properties and elimination pathways. In addition, a trial of clindamycin and TMP-SMX has broad clinical applicability, as both drugs are among the most commonly used agents to treat gram-positive infections in infants and children.

NCT02475876 Bacterial Infections Drug: Clindamycin Drug: trimethoprim-sulfamethoxazole
MeSH:Bacterial Infections

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Number of Subjects Heterozygous for any CYP2C9 Genotype.

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Number of Subjects Homozygous for any CYP3A Family Genotype.

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Number of Subjects Homozygous for any CYP2C9 Genotype.

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Inclusion Criteria: 1. Informed consent from parent or guardian and assent from subject when appropriate 2. Require prevention or treatment of confirmed or suspected infection 3. PMA >36 weeks 4. Able to take oral drugs (TMP-SMX) 5. Sufficient IV access for study drug administration (for clindamycin) and PK sample collection (both drugs) - Exclusion Criteria: 1. History of allergic reactions to study drugs 2. Treatment with the following drugs within 24 hours prior to first dose of clindamycin or expected to receive these drugs during the treatment phase with clindamycin: - CYP3A4 inhibitors (nefazodone, fluconazole, ketoconazole, fluvoxamine, conivaptan, diltiazem, verapamil, aprepitant, ticlopidine, crizotinib, and imatinib), or - CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital, troglitazone, pioglitazone, and St. John's wort).

Primary Outcomes

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Maximum observed plasma concentration at steady state (Cmaxss) - clindamycin

Time: PK sampling taken during 3 continuous days of treatment

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Area under the plasma concentration versus time curve from the start to the end of one dosing interval at steady state (AUCss) - clindamycin

Time: PK sampling taken during 3 continuous days of treatment

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Maximum observed plasma concentration at steady state (Cmaxss) - Trimethoprim-Sulfamethoxazole

Time: PK sampling taken during 3 continuous days of treatment

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Area under the plasma concentration versus time curve from the start to the end of one dosing interval at steady state (AUCss) - Trimethoprim-Sulfamethoxazole

Time: PK sampling taken during 3 continuous days of treatment

Secondary Outcomes

Description: Number of AEs and SAEs reported during (3 continuous days) and up to 30 days after study drug administration

Measure: Number of reported AEs and SAEs

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Heterozygous for any CYP3A Family Genotype

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Heterozygous for any CYP2C9 Genotype

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Homozygous for any CYP3A Family Genotype

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Homozygous for any CYP2C9 Genotype

Time: 33 days

2 Investigation of the Possible Role of Genetic Polymorphism in Certain Metabolizing Enzymes and Membrane Transporters on Both Plasma Level and Molecular Response of Imatinib in Patients With Chronic Myeloid Leukemia

Imatinib, the tyrosine kinase inhibitor, is used for treatment of Philadelphia positive chronic myeloid leukemia. Despite its efficacy and favorable pharmacokinetic profile, there is a large inter-individual variability in imatinib plasma concentrations, which may lead to treatment failure and disease progression. Polymorphisms in genes related to absorption, distribution, metabolism and excretion of imatinib may affect the bioavailability and consequently the response to the drug. The study aims to investigate the possible effect of genetic polymorphisms in certain metabolizing enzymes [CYP3A5*3 (rs776746), CYP2C8*3 (rs11572080 and rs10509681)] and membrane transporters [ABCB1 2677G>T/A (rs2032582) and SLC22A1 1222A > G (rs628031)] by PCR on the plasma level (by HPLC-UV) and molecular response (MMR) of imatinib in patients with CML. The study also aims to provide CML patients with a personalized treatment option, thereby probably improving the response and reducing the side effects.

NCT03262974 Chronic Myeloid Leukemia Diagnostic Test: PCR Diagnostic Test: HPLC-UV
MeSH:Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO:Chronic myelogenous leukemia Leukemia Myeloid leukemia

The study aims to investigate the possible effect of genetic polymorphisms in certain metabolizing enzymes [CYP3A5*3 (rs776746), CYP2C8*3 (rs11572080 and rs10509681)] and membrane transporters [ABCB1 2677G>T/A (rs2032582) and SLC22A1 1222A > G (rs628031)] by PCR on the plasma level (by HPLC-UV) and molecular response (MMR) of imatinib in patients with CML.

Primary Outcomes

Description: A major molecular response (MMR) to imatinib therapy is defined as a BCR-ABL1 RNA level ≤ 0.1% on the International Scale (a consensus standardized measurement scale intended to allow direct comparison of BCR-ABL1 RNA levels in any laboratory adopting its use). The International Scale was specifically designed so that, by definition, 100% is the median pretreatment baseline level of BCR-ABL1 RNA in early chronic phase CML and a 1,000-fold reduction from baseline is defined as 0.1% (MMR) (Press,

Measure: Major molecular response to imatinib

Time: 12 months from starting the drug

3 Federal Cardiomonitoring System. Determination of the Efficiency of a Single-lead ECG Recorded With CardioQVARK Cardiac Monitor in Order to Detect Atrial Fibrillation in Primary Health Centers.

This interventional prospective multicenter nonrandomized clinical and epidemiological study is the first Russian study aimed at evaluating the effectiveness of a single-lead electrocardiography device (CardioQVARK) in screening for atrial fibrillation in primary health care.

NCT04204330 Atrial Fibrillation Device: CardioQvark cardiac monitor and software, single-lead ECG
MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation

For new oral anticoagulants - rs2244613 of the gene CES1, rs1045642 (C3435T), rs1128503 (C1236T), rs2032582 (G2677T / А) of the gene ABCB1, rs2231142 (С421А, Q141K) of the gene ABCG2, rs776746 (A6986G * 399 CYP3 CYP3) CYP3A4.. Inclusion Criteria: Men and women aged 18 to 96 years who have one or more of the following risk factors: - hypertonic disease - history of ischemic stroke or transient ischemic attacks - type 1 and type 2 diabetes - 1-3 degrees obesity - heart failure or the presence of a clinic to reduce exercise tolerance associated with shortness of breath - coronary heart disease or the presence of symptoms of chest pain, in the absence of an established diagnosis of coronary heart disease - the presence of peripheral arterial atherosclerosis - the presence of a clinic of interruptions in the work of the heart (bouts of rapid, irregular heartbeats, pauses in work of heart) Non-inclusion criteria: - Acute coronary syndrome - Acute ischemic or hemorrhagic stroke - Acute psychosis - The presence of severe concomitant diseases with an expected life expectancy of less than 2 years Exclusion Criteria: Refusal of further participation in the study Inclusion Criteria: Men and women aged 18 to 96 years who have one or more of the following risk factors: - hypertonic disease - history of ischemic stroke or transient ischemic attacks - type 1 and type 2 diabetes - 1-3 degrees obesity - heart failure or the presence of a clinic to reduce exercise tolerance associated with shortness of breath - coronary heart disease or the presence of symptoms of chest pain, in the absence of an established diagnosis of coronary heart disease - the presence of peripheral arterial atherosclerosis - the presence of a clinic of interruptions in the work of the heart (bouts of rapid, irregular heartbeats, pauses in work of heart) Non-inclusion criteria: - Acute coronary syndrome - Acute ischemic or hemorrhagic stroke - Acute psychosis - The presence of severe concomitant diseases with an expected life expectancy of less than 2 years Exclusion Criteria: Refusal of further participation in the study Atrial Fibrillation Atrial Fibrillation This is an interventional, prospective, multicenter, nonrandomized clinical and epidemiological study.

Primary Outcomes

Description: Total number of AF cases newly diagnosed during the study period.

Measure: Total number of AF cases newly diagnosed during the study period.

Time: Through study completion, an average of 1 year

Description: Number of patients who, for the first time ever, were assigned to anticoagulation therapy.

Measure: Number of patients who, for the first time ever, were assigned to anticoagulation therapy.

Time: Through study completion, an average of 1 year

Description: Assessed using data obtained from pharmacokinetic analysis. International normalised ratio (INR) - target range from 2 to 3.

Measure: Compliance to anticoagulation therapy for warfarin.

Time: 6 months after administration of anticoagulants

Description: Assessed using data obtained from pharmacokinetic analysis. Quantitative determination of the concentration of drugs in the blood (blood sampling three hours after taking the drug).

Measure: Compliance to anticoagulation therapy for new oral anticoagulants.

Time: 6 months after administration of anticoagulants

Description: Evaluated as incremental cost-effectiveness ratio of screening per quality adjusted life year gained, and per stroke avoided.

Measure: Cost-effectiveness of using the single-lead CardioQVARK ECG device in screening for AF in primary health care.

Time: Through study completion, an average of 1 year

Secondary Outcomes

Description: Mean time to diagnosis.

Measure: Mean time to diagnosis.

Time: Through study completion, an average of 1 year

Description: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 1.

Measure: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 1.

Time: Through study completion, an average of 1 year

Description: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 2.

Measure: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 2.

Time: Through study completion, an average of 1 year

Description: Defined as frequency of ischemic stroke or transient ischemic attack in patients with newly diagnosed AF and assigned anticoagulants.

Measure: Incidence of ischemic stroke or transient ischemic attack after enrollment in the study.

Time: Through study completion, an average of 1 year

Description: Defined as frequency of massive hemorrhage in patients with newly diagnosed AF and assigned anticoagulants.

Measure: Incidence of massive hemorrhage after enrollment in the study.

Time: Through study completion, an average of 1 year

Description: Defined as frequency of hemorrhagic stroke in patients with newly diagnosed AF and assigned anticoagulants.

Measure: Incidence of hemorrhagic stroke after enrollment in the study.

Time: Through study completion, an average of 1 year

Description: For warfarin - CYP2C9 (CYP2C9 * 2, CYP2C9 * 3), VKORC1 (1 marker), CYP4F2 (1 marker), GGCX (1 marker). For new oral anticoagulants - rs2244613 of the gene CES1, rs1045642 (C3435T), rs1128503 (C1236T), rs2032582 (G2677T / А) of the gene ABCB1, rs2231142 (С421А, Q141K) of the gene ABCG2, rs776746 (A6986G * 399 CYP3 CYP3) CYP3A4.

Measure: Pharmacogenetic testing by polymorphic markers

Time: 6 months after administration of anticoagulants


HPO Nodes