A Study to Evaluate Vitamin B3 Derivative to Treat Mitochondrial Myopathy

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of Nicotinamide Riboside (NR) supplement in adult-onset symptoms of mitochondrial myopathy.

Official Title
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Randomized, Double-blinded, Placebo-controlled Study Evaluating the Efficacy of Nicotinamide Riboside (NR) - a Vitamin B3 Derivative - for Treatment of Mitochondrial Myopathy Disorder

Conditions
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Mitochondrial Myopathy

Intervention / Treatment
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* Dietary Supplement: Nicotinamide Riboside
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biochemically and/or genetically confirmed or confirmed primary mitochondrial myopathy based on published diagnostic criteria. Biochemically confirmed mitochondrial disorder would mean that the patient meets clinical criteria and has either biopsy or biochemical testing that supports the diagnosis. Confirmed mitochondrial disorder means that the patient meets published clinical criteria for the diagnosis and has also had confirmatory genetic testing for the disorder type. Agreed to avoid vitamin supplementation or nutritional products with vitamin B3 forms 14 days prior to the enrollment and during the study in order to not exceed 200 mg/day of vitamin B3 derivatives intake. Female of childbearing potential agreed to use effective contraception throughout the study. Written, informed consent to participate in the study. Exclusion Criteria: Unwilling to comply with the follow-up schedule. Inability or refusal to give informed consent by the patient or a legally authorized representative. Known pregnancy or breastfeeding. Concurrent participation in another investigational drug study or within washout period of treatment. Presence of other medical symptoms or condition, which may interfere with interpretation of outcome measures as determined by the study PI. Clinical / Laboratory Exclusion Criteria: Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min. Patients in permanent Renal Replacement Therapy. Serum alkaline phosphatase 50% above normal limit. Serum aspartate transaminase 50% above normal limit. Serum Thyroxine (T4) 50% above or below normal limit. Serum Thyroid Stimulating Hormone (TSH) 50% above or below normal limit. Severe anemia with Hb < 7g/dL. Severe leukocytosis with WBC > 15,000/mm^3.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinamide Riboside treatment group<br>Subjects will receive vitamin B3 derivative Nicotinamide Riboside (NR) daily for 12 months | Dietary Supplement: Nicotinamide Riboside<br>* Vitamin B3 derivative; a total of 1000 mg/day in a regimen of 500mg every 12 hours by mouth (either fasting or fed)<br>|
| Placebo Comparator: Placebo Group<br>Subjects will receive a placebo daily for 12 months | Drug: Placebo<br>* Looks exactly like the study drug, but it contains no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in 6-Minute Walk Test Performance | The 6-minute walk test (6MWT) quantifies the distance a person can walk in six minutes. Measured in meters. | Baseline, 6 months, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skeletal muscle function | Measured using the Short Physical Performance Battery (SPPB) score based on timed measures of standing balance, walking speed and ability to rise from a chair. Each of the 3 performance measures will be assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 the inability to complete the test. A summary score (range 0-12) will be subsequently calculated by adding the 3 scores. | Baseline, 6 months, 12 months | 
| Change in skeletal muscle strength | Measured using the strength one repetition maximum (1RM leg press) defined as the maximal weight an individual can lift for only one repetition with correct technique. | Baseline, 6 months, 12 months | 
| Change in isometric strength of trunk flexors | Assessed by generated maximum force against a stationary dynamometer reported in kilograms of force. Trunk flexion strength tested in the supine position with knees slightly bent, arms at side and head in midline. The base of the dynamometer will be placed on the middle of the sternum and the patient will be instructed to exert isometric force by lifting both scapula off the plinth. | Baseline, 6 months, 12 months | 
| Change in isometric strength of trunk extensor muscle | Assessed by generated maximum force against a stationary dynamometer reported in kilograms of force. Trunk extensor muscle strength tested in prone position. The base of the dynamometer will be placed at the level of the T4 spine and the patient instructed to generate an isometric force by lifting the chest off the plinth. After sufficient practice in the standardized positions, 5 trials will be recorded in each position. | Baseline, 6 months, 12 months | 
| Change in maximal oxygen uptake (VO2 max) | Maximal oxygen uptake (VO2 max) test measures the maximum rate of oxygen consumption during incremental exercise (exercise of increasing intensity) and reflects the cardiorespiratory fitness of an individual. Reported in ml/kg/min. | Baseline, 6 months, 12 months |