A Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy (SMA) Patients (S16.003)

OBJECTIVE: To assess the effects of aerobic and strengthening exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients. BACKGROUND: The effect of exercise in Spinal Muscular Atrophy (SMA) has not been formally addressed in a controlled trial. SMA 3 patients represent an ideal target population because their residual strength facilitates endurance and strengthening programs. METHODS: Fourteen participants ages 10-48 years were randomized into two cohorts. The experimental group received 6 months of exercise followed by 6 months of closely monitored ongoing treatment. The control group received 6 months of exercise starting at month 7. Exercise included individualized home-based cycling five-times weekly and strengthening three-times weekly. The primary outcome measure was distance walked during the six-minute walk test (6MWT). Secondary outcome measures included strength, functional measures, and exercise capacity. RESULTS: Twelve participants completed the controlled portion of the study, 9 were followed for 12 months. Falls were the most common adverse event with no difference by group (p = 0.488). Most participants were at least 90% compliant with the exercise prescription over 6 months (n = 9). There were no group changes at 6 or 12 months in the 6MWT, fatigue, or functional measures. There was a positive trend in the exercise group for arm strength (p = 0.080) over 6 months. Percent-predicted VO2 max improved 4.9% in all participants (p = 0.036). Even greater changes (6.6%) were seen in the most compliant participants (p = 0.012). CONCLUSIONS: Daily exercise is safe in ambulatory SMA children and adults, and should be encouraged. We uncovered no deleterious effects on strength or function. Exercise ability in SMA patients improved slowly, which must be accounted for when designing timelines for future clinical trials. Our study suggests that overall fitness in SMA patients improves with sustained aerobic exercise. Disclosure: Dr. Montes has received personal compensation for activities with Isis Pharmeceuticals as a consultant. Dr. Kramer has nothing to disclose. Dr. Dunaway has nothing to disclose. Dr. Montgomery has nothing to disclose. Dr. Carr has received research support from the Agency for Healthcare Research & Quality, the Center for Disease Control & Prevention, and the National Institutes of Health. Dr. Kamil-Rosenberg has nothing to disclose. Dr. Sproule9s spouse holds stock and/or stock options in Pfizer, Inc. Dr. Sproule has received research support from Santhera Pharmaceuticals and PTC Therapeutics Inc. Dr. Strauss has nothing to disclose. Dr. Garber has nothing to disclose. Dr. De Vivo has received personal compensation for activities with Isis Pharmaceuticals and Ultragenyx Pharmaceuticals.