Neuromuscular Disease
Conditions
Keywords
A3243G Mitochondrial DNA Point Mutation
Brief summary
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.
Interventions
DRUGA0001 (alpha-tocopherolquinone)
28 days (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.
DRUGPlacebo
28 days of placebo oral capsules. Treatment taken twice daily with meals.
Sponsors
Penwest Pharmaceuticals Co.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement in the rate of ATP recovery (Vmax) in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) | Baseline and Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| Exercise tolerance as measured by a 6 minute walk test | Baseline, Day 14 and Day 28 |
| 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 | Baseline and Day 28 |
| Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels | Baseline, Day 14 and Day 28 |
| Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI) | Baseline and Day 28 |
| Quality of life (SF-36® Health Survey Questionnaire) | Baseline and Day 28 |
| Global impression of clinical severity | Baseline, Day 14 and Day 28 |
| Modified fatigue impact scale | Baseline, Day 14 and Day 28 |
| Mitochondrial disease severity (NMDAS) | Baseline and Day 28 |
Countries
United Kingdom
Outcome results
None listed