SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation A3243G

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 6 clinical trials

Clinical Trials


1 A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of ME1100 Inhalation Solution (Arbekacin Inhalation Solution) Administered to Healthy Volunteers

This is a single-center, randomized, double-blind, placebo-controlled, sequential group study. The primary objective of this study is to assess the tolerability and safety of single doses of ME1100 inhalation solution (orally inhaled arbekacin). The secondary objective is to determine the systemic exposure to, and urinary elimination of, ME1100.

NCT01907776
Conditions
  1. Healthy
Interventions
  1. Drug: ME1100 inhalation solution
  2. Drug: ME1100 placebo inhalation solution

heteroplasmy) suggestive of increased risk of hearing loss (MT-RNR1 [A1555G] for mitochondrial 12S ribosomal RNA gene or MT-TS1 [A3243G] for mitochondrial transfer RNA serine 1) - History of parent, sibling or parental sibling reporting hearing loss before age 65 years - History of malignancy - History of clinically significant alcohol or drug abuse - History within last 6 months or current use of any tobacco product including e-cigarettes - Positive drug screen for drugs of abuse - Positive test for HIV, Hepatitis B or Hepatitis C - Use of any prescription or over-the-counter medications (except oral or hormonal contraceptives), herbal supplements, or vitamins within 14 days of Visit 2 - Known hypersensitivity to any aminoglycoside or bacitracin antibiotic - Female of childbearing potential with a positive urine pregnancy test, or currently breast feeding. --- A1555G --- --- A3243G ---

Primary Outcomes

Measure: Number of participants with adverse events

Time: from Baseline to Day 8-10

Measure: Number of participants with abnormal physical examinations

Time: from Baseline to Day 8-10

Measure: Number of participants with abnormal 12-lead electrocardiograms

Time: from Baseline to Day 8-10

Measure: Number of participants with abnormal vital signs

Time: from Baseline to Day 8-10

Measure: Number of participants with abnormal safety laboratory measurements

Time: from Baseline to Day 8-10

Secondary Outcomes

Measure: Serum Concentration of ME1100

Time: 5, 15, 30 minutes and 1, 2, 3, 4, 6, 8, 12, 18 and 24 hours post START of dosing

Measure: Urinary elimination of ME1100

Time: 0-6, 6-12, 12-24, 24-48 and 48-72 hours after single dosing

2 An Open-label, Single Dose Study to Assess Intrapulmonary Pharmacokinetics of ME1100 Inhalation Solution Administered to Healthy Volunteers

This is a single-center, open-label, single-dose study. The primary objective is to determine Epithelial Lining Fluid (ELF) levels of ME1100 after a single orally inhaled dose. The secondary objectives are to determine systemic exposure to inhaled ME1100 and to assess tolerability and safety of a single dose of ME1100 inhalation solution.

NCT01961830
Conditions
  1. Healthy
Interventions
  1. Drug: ME1100 inhalation solution

heteroplasmy) suggestive of increased risk of hearing loss (MT-RNR1 [A1555G] for mitochondrial 12S ribosomal RNA gene or MT-TS1 [A3243G] for mitochondrial transfer RNA serine 1) - History of parent, sibling or parental sibling reporting hearing loss before age 65 years - History of malignancy - History of clinically significant alcohol or drug abuse - History within last 6 months or current use of any tobacco products including e-cigarettes. --- A1555G --- --- A3243G ---

Primary Outcomes

Description: Each subject will undergo fiber-optic bronchoscopy for the collection of bronchoalveolar lavage fluid at one of the following time points:5 minutes after END of dosing, 0.5, 1, 3, 6 and 12 hrs post START of dosing.

Measure: Pharmacokinetics profile in ELF

Time: 0-12 hours after START of Dosing

Secondary Outcomes

Measure: Serum Concentration of ME1100

Time: 2, 5, 10 minutes after END of dosing, 0.5, 1, 3, 6 and 12 hrs post START of dosing

Measure: Number of participants with abnormal safety laboratory measurements

Time: from Baseline to Day 3

3 Investigation of Clinical Syndromes Associated With mtDNA Point Mutations: MELAS/DCA Clinical Trial

Patients with the MELAS syndrome experience devastating mental impairment. This study will evaluate the effectiveness of the drug dichloroacetate (DCA) to reduce the symptoms of MELAS.

NCT00068913
Conditions
  1. MELAS Syndrome
Interventions
  1. Drug: Dichloroacetate
MeSH:MELAS Syndrome Syndrome

Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol MELAS Syndrome MELAS Syndrome Syndrome Although many organ systems are affected by mitochondrial (mt) DNA point mutations, the nervous system is particularly vulnerable. --- A3243G ---

Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol Inclusion Criteria - A3243G mtDNA point mutation or maternally related to someone who has the mutation - Symptomatic with MELAS, including previous seizure or stroke - Certain laboratory values - Ability to comply with the study protocol MELAS Syndrome MELAS Syndrome Syndrome Although many organ systems are affected by mitochondrial (mt) DNA point mutations, the nervous system is particularly vulnerable. --- A3243G --- --- A3243G ---

Patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome have the A3243G point mutation and elevated brain lactate levels. --- A3243G ---

Patients with the A3243G mitochondrial mutation and who have had either a stroke or a seizure will be enrolled in this study. --- A3243G ---


4 Pilot Study to Investigate the Efficacy of L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome.

MELAS patients suffer from exercise intolerance, weakness, poor vision or blindness, poor growth, developmental delay, and deafness. They also have unique 'stroke-like' episodes (SLEs) which are not due to blockages of large or medium arteries. These 'strokes' are thought to be due to energy failure of very small brain blood vessels combined with energy failure in the mitochondria (cell battery) of the brain cells, especially in the back region of the brain in the vision centre. This leads to visual loss and paralysis. The overall goal of this study is to better understand the mechanism of these SLEs at the level of the brain cells and small blood vessels.

NCT01603446
Conditions
  1. MELAS Syndrome
Interventions
  1. Drug: L-Arginine
MeSH:MELAS Syndrome Syndrome

Inclusion Criteria: Experimental Siblings with MELAS (A3243G) syndrome - 17-23 years - Followed Neurometabolic Clinic at the Hospital for Sick Children will be studied. --- A3243G ---

Primary Outcomes

Description: We will study exercising quadriceps using our MR-compatible up-down ergometer and our well established aerobic exercise protocol at 65 % of maximal voluntary contraction.

Measure: Muscle function investigation via 31P-Magnetic resonance spectroscopy

Time: 60 to 105 minutes post dose

Secondary Outcomes

Description: Maximal incremental cycle ergometry is conducted in our CardioRespiratory Exercise Lab at HSC by our established protocols (26). Serum CK and quantitative AA (for arginine, ornithine and citrulline) will be measured pre- and post- exercise as well as eNO in order to correlate aerobic exercise parameters with serum arg and eNO levels..

Measure: Total body maximal aerobic capacity

Time: 60-75 mins post dose

Description: Functional MRI-Blood oxygen level dependent (BOLD) of brain

Measure: CerebroVascular Reactivity

Time: 75-105 mins post dose

Description: eNO will be measured using single breath on-line measurements for the assessment of lower airway Nitric Oxide

Measure: Exhaled Nitric Oxide (eNO)

Time: 75 mins pre dose, 75 mins post dose

5 A Phase 2a, Double Blind, Randomized, Placebo-controlled, 28 Day, Two-arm, Parallel Group Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation and Evidence of Impaired Mitochondrial Function

This is a phase 2a, double-blind, placebo-controlled, single-center study. Twenty-one patients who qualify for the study will be randomly assigned to either active drug or placebo. The study will take place at Newcastle University. Patients will have a 66% chance of getting active drug. Patients will be required to take study treatment orally twice a day for 28 days. A baseline visit will occur within 21 days of screening visit. All patients will be followed for 1 week after completion of study or early withdrawal from the study.

NCT01074359
Conditions
  1. Neuromuscular Disease
Interventions
  1. Drug: A0001 (alpha-tocopherolquinone)
  2. Drug: Placebo
MeSH:Neuromuscular Diseases

A Phase 2a, Double Blind, Randomized, Placebo-controlled, 28 Day, Two-arm, Parallel Group Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation and Evidence of Impaired Mitochondrial Function. --- A3243G ---

Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation This is a phase 2a, double-blind, placebo-controlled, single-center study. --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G --- --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G --- --- A3243G --- --- A3243G ---

Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Inclusion Criteria: - Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation - PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: - Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study - Use of any investigational product within the past 30 days Neuromuscular Disease Neuromuscular Diseases null --- A3243G --- --- A3243G --- --- A3243G --- --- A3243G ---

Primary Outcomes

Measure: Improvement in the rate of ATP recovery ("Vmax") in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS)

Time: Baseline and Day 28

Secondary Outcomes

Measure: Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI)

Time: Baseline and Day 28

Measure: Exercise tolerance as measured by a 6 minute walk test

Time: Baseline, Day 14 and Day 28

Measure: Improvement in the rate of Maximal ATP recovery (Vmax) as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) MRI of calf muscle during a standardized isolated calf muscle procedure of 2 bouts of plantar flexion exercise

Time: Baseline and Day 28

Measure: Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels

Time: Baseline, Day 14 and Day 28

Measure: Mitochondrial disease severity (NMDAS)

Time: Baseline and Day 28

Measure: Quality of life (SF-36® Health Survey Questionnaire)

Time: Baseline and Day 28

Measure: Global impression of clinical severity

Time: Baseline, Day 14 and Day 28

Measure: Modified fatigue impact scale

Time: Baseline, Day 14 and Day 28

6 A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes

The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.

NCT00887562
Conditions
  1. MELAS Syndrome
Interventions
  1. Drug: Idebenone
  2. Drug: Idebenone
  3. Other: Placebo
MeSH:MELAS Syndrome Brain Diseases Acidosis Acidosis, Lactic
HPO:Acidosis Encephalopathy Lactic acidosis Metabolic acidosis

Inclusion Criteria: - Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss) - Cerebral lactate level equal to or greater than 5.0 i.u. at baseline - Patients at least 8 and < 65 years of age at baseline - Patients with a body weight > 37 kg/82 lbs at baseline - Stable co-medication/vitamins/supplements within 1 month prior to baseline - Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication - Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion Criteria: - Contraindication to MRS (e.g. --- A3243G ---

metal implant, claustrophobia) - Stroke like event within 2 months prior to baseline - Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline - Inadequate contraception use - Pregnancy and/or breast-feeding - Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine - Current abuse of drugs or alcohol - Participation in a trial of another investigational drug within the last month - Other factor that, in the investigator's opinion, excludes the patient from entering the study Inclusion Criteria: - Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss) - Cerebral lactate level equal to or greater than 5.0 i.u. at baseline - Patients at least 8 and < 65 years of age at baseline - Patients with a body weight > 37 kg/82 lbs at baseline - Stable co-medication/vitamins/supplements within 1 month prior to baseline - Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication - Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion Criteria: - Contraindication to MRS (e.g. --- A3243G ---

Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group. --- A3243G ---

The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). --- A3243G ---

Primary Outcomes

Description: To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on cerebral lactate concentration as measured by magnetic resonance spectroscopy (MRS)

Measure: Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)

Time: Up to 4 weeks from baseline

Secondary Outcomes

Description: To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration

Measure: Mean Change in Venous Lactate Concentration

Time: Up to 4 weeks from baseline

Description: To assess changes following 1 month treatment with 2 different doses of idebenone with that of placebo in fatigue as assessed by the Fatigue Severity Scale (FSS). Scale score minimum is 9 (least fatigue) and maximum is 63 (maximum fatigue). Scores of 36 or less indicate possibility that patient may not be suffering from fatigue, while scores 36 and over suggest suffering from fatigue

Measure: Mean Change in Score on the Fatigue Severity Scale (FSS)

Time: Baseline and Week 4


HPO Nodes


HP:0001298: Encephalopathy
Genes 363
GABRB1 CDKL5 ACSF3 ATAD3A DPM2 NAGS EEF1A2 TCF4 ND6 NDUFS4 GALC TRNL1 TREX1 TRNK NDUFAF4 AMT TRNC NECAP1 NDUFA11 TSFM LYRM7 NDUFB9 CNKSR2 D2HGDH TWNK SLC25A1 GABRG2 NECAP1 STAG1 TRNS2 ATP5F1A ITPA ARHGEF9 UGDH CNTNAP2 GABRA1 CACNA1A SLC2A1 MDH1 NBAS AARS1 NDUFS8 GCSH DNM1 STXBP1 AMACR GBA ND1 ATP1A3 NDUFAF2 CPT2 TCF4 NDUFS6 NDUFS6 GABRG2 NRXN1 SLC19A3 KCNT2 ACY1 PNPT1 SYNJ1 CPT2 CPLX1 COQ4 ARHGEF9 AARS1 ADAM22 AP3B2 WWOX GABRB3 DCX SYNJ1 DNM1L NDUFA6 GLDC TIMM50 NDUFS1 SLC13A5 CAD ROGDI NUS1 GRIN1 KCNQ2 NOTCH3 PAFAH1B1 NDUFAF1 COX1 PNPO ATP6V1A MEF2C NADK2 BSCL2 GABBR2 ARV1 HCN1 NDUFA6 TH PIGA ATP5F1A MTHFR CLTC SZT2 ND6 NDUFS2 NDUFV2 NDUFAF5 DLD SIK1 ND3 GABRA5 MST1 MECP2 SLC25A20 GPT2 SERAC1 TK2 MDH2 ACOX1 NDUFS3 FBLN1 SLC1A2 RANBP2 GABRB2 KCNQ5 CACNA1B PCK1 TRNQ PNPO TRNW RNF13 NDUFS7 BCS1L DNM1 NDUFA1 SCN3A COG8 PCCA NUBPL COX15 KMT2E PTPN23 TRIT1 SCN1A COX2 NTRK2 HNRNPU SLC25A12 PACS2 SERPINI1 COQ2 CDK19 TRNW TRAK1 ATP5F1D PLCB1 NDUFB3 COX3 GRIN2D COG8 HADH SUCLG1 COQ5 ACAD9 SYNGAP1 CHD2 CHD2 DENND5A RNASEH2B EEF1A2 NDUFB10 ACTL6B FADD KYNU SH2D1A RNF13 SLC12A3 KCNB1 CYFIP2 NDUFA11 NDUFS3 KCNA2 RINT1 YWHAG UNC80 CACNA2D2 TSEN54 SLC35A2 NTRK2 SLC19A3 TBC1D24 SLC25A13 CLCNKB TRNS1 IBA57 CNPY3 TRNH TBCE COX1 PARS2 SLC22A5 NADK2 LIPT2 NAXE GABRB2 PNKP DOCK7 ND2 PPP3CA NDUFAF2 CLCN4 NRXN1 WDR45 PHACTR1 NDUFS7 PSAP GABRB3 GCDH NDUFV1 TBC1D24 CLP1 ND1 GLUL TBCK ND4 GLS CPT1A FOXRED1 STAT2 DGUOK AP2M1 TRNF CACNA1E SCN2A CCDC88A DALRD3 CYFIP2 KCNA2 FADD TMEM126B WWOX KCNA2 TRNV CLPB TRNQ TRAK1 ARV1 RNASEH2C MAPK10 PIGP UBA5 HTRA1 TRNS1 TRAPPC12 COX2 SLC25A15 CUX2 CHD2 GRIN2B SLC25A15 BSCL2 NDUFB11 COQ9 CARS2 PARS2 HIBCH KCNQ2 GRIN2D SUCLA2 SCN8A CACNA1A NDUFAF8 KYNU TMEM70 PCCB NDUFAF4 SLC25A22 SCN1A ACAD9 SPTAN1 TRNK CYTB GABRA2 ND5 DHDDS ACY1 TGFB1 FBXL4 MMACHC HSD17B10 SLC22A5 CYC1 SLC35A1 SYNGAP1 SIK1 GBA SLC1A2 FCSK HADH TRNL1 UBA5 SZT2 ST3GAL3 SCN1B AP3B2 GUF1 TRNF NUS1 ALMS1 NEUROD2 TUFM NDUFV2 ND5 GNAO1 HMGCL PPP3CA STXBP1 FRRS1L FGF12 BOLA3 TRNS2 DNM1 PRNP TIMMDC1 ETHE1 CARS2 ND1 DLD SLC6A9 ETHE1 LIAS SCN3A NAXD MPC1 ZNHIT3 UGT1A1 TBCD SLC13A5 ATAD1 NDUFAF3 KCNB1 ALG9 GPR35 KCNT1 SCN2A ARX DHDDS CACNA1B NDUFS4 NDUFAF1 RANBP2 NDUFB3 COX3 SCN8A HCN1 ASNS ATP6V1A TBCE GLYCTK SLC6A1 XIAP PMPCB CUX2 FGF12
Protein Mutations 1
A3243G
SNP 0