Oxidative Capacity and Exercise Tolerance in Ambulatory SMA

Study Overview
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Brief Summary
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This proposal will focus on (1) estimating oxidative capacity of specific muscle groups during exercise using near infrared spectroscopy and (2) describing body composition to better understand exercise capacity and mitochondrial function in ambulatory spinal muscular atrophy (SMA) patients and disease controls. It is a 6-month observational study including 14 ambulatory SMA patients, 14 ambulatory patients with mitochondrial myopathy, and 14 healthy controls.

Detailed Description
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Spinal Muscular Atrophy (SMA) is a progressive, recessively-inherited neuromuscular disease characterized by weakness and muscle atrophy due to the loss of spinal cord motor neurons. The results from this study would provide preliminary data, using non-invasive methods, on oxidative capacity in ambulatory SMA patients and disease controls to aid in the design of exercise intervention studies. Furthermore, this information would link previous laboratory and preclinical findings of mitochondrial depletion in SMA to the clinical condition and provide important information for future studies designed to improve oxidative capacity and fitness in SMA patients.

Official Title
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Evaluation of Oxidative Capacity and Exercise Tolerance in Ambulatory Patients With Spinal Muscular Atrophy (SMA)

Conditions
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Spinal Muscular Atrophy Type 3, Mitochondrial Myopathy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the following categories: Genetic confirmation of SMA with laboratory documentation of homozygous deletion of SMN1 exon 7; Genetic confirmation of mitochondrial myopathy or evidence from muscle biopsy confirming the diagnosis; or Healthy individuals. Able to walk independently at least 25 meters, and able to tread a stationary cycle ergometer. Exclusion Criteria: Unable to walk 25 meters independently. Use of investigational medications intended for the treatment of SMA within 30 days prior to study entry. The presence of any contraindication to exercise according the ACSM criteria. Patients with and without Spinraza treatment are eligible.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| spinal muscular atrophy<br>ambulatory children and adults ages between 8 and 55 years old by the time of enrollment with laboratory documentation of homozygous deletion of SMN1 exon 7 | |
| mitochondrial myopathy<br>ambulatory children and adults ages between 8 and 55 years old by the time of enrollment with genetic confirmation or evidence from muscle biopsy confirming the diagnosis | |
| control<br>The healthy control group will be age and gender-matched to the SMA and mitochondrial myopathy groups as best as possible. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in NIRS derived index of muscle oxygen extraction | Near Infrared Spectroscopy (NIRS) is a simple, non-invasive method to measure oxygen in muscle and other tissues in vivo. | baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak oxygen uptake (V02 max) | Participants will undergo an exercise stress test performed by a clinical exercise physiologist using an electronically-braked recumbent cycle ergometer to determine peak oxygen uptake (VO2 max). | baseline, 6 months | 
| Change in Distance walked during the Six Minute Walk Test (6MWT) | 6MWT is an objective evaluation of functional exercise capacity, measures the maximum distance a person can walk in six minutes over a 25-meter linear course. | baseline, 6 months | 
| Change in Lean body mass assessed with Dual Energy X-ray Absorptiometry (DEXA) | Dual-Energy X-ray Absorptiometry (DEXA) is a method of estimating bone and lean body mass by comparing the absorption of two distinct energy level beams at 46.8 keV and 80 keV, which are effective at differentiating soft tissue and bone. A standard DEXA scan will be performed in supine. | baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ambulation, spinal muscular atrophy, oxidative capacity, exercise tolerance, mitochondrial myopathy, SMA, six minute walk test, neuromuscular disease, exercise, mitochondria, cycle ergometry, near infrared spectroscopy