Exercise training and cognition in multiple sclerosis: The GET Smart trial protocol.

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Publication Date


Publication Title

Contemp Clin Trials


washington; seattle; swedish neuro; Aerobic; Cognition; Exercise; Multiple sclerosis; Research design


BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) causes cognitive impairment in approximately 50% of cases. Disease modifying medications and cognitive rehabilitation produce only small positive effects on cognition in MS. Converging animal and human research suggests that aerobic exercise may improve cognition in people with MS, but definitive trials are lacking. We describe the design of the GET Smart study, a randomized controlled trial comparing the effects of aerobic exercise versus stretching and toning on cognition in MS.

METHODS: The study is a single-blind, parallel group randomized (1:1) controlled trial that compares aerobic exercise training with an active control group consisting of stretching and toning exercises for improving cognition. Participants are nondepressed, ambulatory, non-exercising adults with MS aged 18-54 years who have below average cognitive processing speed. Both treatments were designed to generate equivalent outcome expectancies and entailed supervised, progressive exercise programs, 3 times per week for up to 40 min over a 6 month period.

PROJECTED PATIENT OUTCOMES: The primary hypothesis is that the aerobic training group will demonstrate significantly greater cognitive processing speed compared with the control group at the end of the treatment phase (6 months) as measured by a composite of the Paced Auditory Serial Additon Test and the oral Symbol-Digit Modalities Test using intent-to treat analyses. Secondary outcomes are neuropsychological functioning and cardiorespiratory fitness as well as participant reported outcomes such as depression, sleep, and fatigue. Study findings will inform future research, patient education, clinical care and policymaking.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02106052.

Clinical Institute

Orthopedics & Sports Medicine

Clinical Institute

Neurosciences (Brain & Spine)






Behavioral Health