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Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative?

ABSTRACT: The benefits of exercise on long-term health and well-being are well established. The possible benefits of exercise in Spinal Muscular Atrophy (SMA) have not been explored in a controlled clinical trial format.To assess the effects of exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients.Fourteen participants, ages 10-48 years, were randomized to control and exercise cohorts after a 1 month lead-in period. The exercise group received 6 months of intervention. Thereafter, both groups received the intervention for the remaining 12 months. Participants were monitored for a total of 19 months. Exercise included individualized home-based cycling and strengthening. The primary outcome measure was distance walked during the six-minute walk test (6MWT). Secondary outcomes included strength, function, exercise capacity, quality of life and fatigue.Twelve participants completed the first 7 months of the study, and 9 completed all 19 months. At baseline, the groups were similar on all clinical variables. There were no group changes at any time point in the 6MWT, fatigue, or function. Percent-predicted VO2 max improved 4.9% in all participants in 6 months (p?=?0.036) (n?=?10).Daily exercise is safe in ambulatory SMA and should be encouraged. We did not uncover any deleterious effects on strength, function, or fatigue. Our study documented a reduction in oxidative capacity and a blunted conditioning response to exercise possibly representing an important insight into underlying pathophysiological mechanisms. These findings also may be linked causally to mitochondrial depletion in SMA and warrant further study.

SUBMITTER: Montes J

PROVIDER: S-EPMC5240606 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative?

Montes Jacqueline J Garber Carol Ewing CE Kramer Samantha S SS Montgomery Megan J MJ Dunaway Sally S Kamil-Rosenberg Shirit S Carr Brendan B Cruz Rosangel R Strauss Nancy E NE Sproule Douglas D De Vivo Darryl C DC

Journal of neuromuscular diseases 20151001 4

<h4>Background</h4>The benefits of exercise on long-term health and well-being are well established. The possible benefits of exercise in Spinal Muscular Atrophy (SMA) have not been explored in a controlled clinical trial format.<h4>Objective</h4>To assess the effects of exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients.<h4>Methods</h4>Fourteen participants, ages 10-48 years, were randomized to control and exercise cohorts after a 1 month lead-in period ...[more]

PMID: 27858749

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Project description:Hereditary proximal spinal muscular atrophy causes weakness and increased fatigability of repetitive motor functions. The neuromuscular junction is anatomically and functionally abnormal in patients with spinal muscular atrophy. Pharmacological improvement of neuromuscular transmission may therefore represent a promising additional treatment strategy. We conducted a Phase II, monocentre, placebo-controlled, double-blind, cross-over trial with the acetylcholinesterase inhibitor pyridostigmine in treatment-naïve patients with spinal muscular atrophy types 2-4. We investigated the safety and efficacy of pyridostigmine on fatigability and motor function. Each participant received pyridostigmine and a placebo for 8 weeks, in random order. Primary outcomes were the repeated nine-hole peg test for fatigability and motor function measure. Secondary outcomes were patient-reported effects, endurance shuttle test combined scores and adverse events. We included 35 patients. For the repeated nine-hole peg test, the mean difference was 0.17 s/trial (95% confidence interval: -1.17-1.49; P = 0.8), favouring placebo, and for the motor function measure, 0.74% (95% confidence interval: 0.00-1.49; P = 0.05), favouring pyridostigmine. Around 74% of patients reported medium-to-large beneficial effects of pyridostigmine on fatigability, compared with 29.7% in the placebo arm. This was paralleled by a reduced dropout risk of 70% on the endurance shuttle test combined scores (hazard ratio: 0.30; 95% confidence interval: 0.15-0.58) under pyridostigmine. Adverse events, mostly mild and self-limiting, occurred more frequently under pyridostigmine. No serious adverse events related to the study medication were observed. Patients with spinal muscular atrophy tolerated pyridostigmine well. There were no significant differences in primary outcomes, but the self-reported reduction of fatigability and improved endurance shuttle test combined score performance suggest that pyridostigmine may be useful as an additional therapy to survival motor neuron-augmenting drugs. Trial registration number: EudraCT: 2011-004369-34, NCT02941328.

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Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative?

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Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative?

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