Aerobic Exercise for Remyelination in Multiple Sclerosis

Aerobic Exercise to Improve Mobility in Multiple Sclerosis: Optimizing Design and Execution for a Full-scale Multimodal Remyelination Clinical Trial

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Portland VA Medical Center, Oregon Clinical and Translational Research Institute, Myelin Repair Foundation, EMD Serono, Medical Research Foundation, Oregon

This is a clinical trial to determine the feasibility of a stationary aerobic cycling intervention and explore if aerobic exercise independently promotes remyelination in people with multiple sclerosis (MS).

Multiple sclerosis (MS) is the most common non-traumatic disabling neurologic condition of young adulthood, affecting more than 2.5 million people worldwide. Permanent disability in MS is caused by recurrent demyelination due to episodic inflammation, followed by neuronal damage, axonal degeneration, and progressive failure of remyelination. There is an urgent need to restore activity and participation in people with MS (pwMS), and remyelination is the most promising therapeutic strategy to accomplish this goal. Remyelination in pwMS will likely require integration of pharmacologic and rehabilitative approaches to ensure effective remyelination of appropriate neural pathways. Aerobic exercise is an ideal complement to remyelinating medications because aerobic exercise 1) improves walking function in pwMS, and 2) promotes remyelination in animal models both independently and synergistically with medications. However, there are many unknowns that need to be addressed before aerobic exercise can be explored in multimodal clinical trials for remyelination. First, it is imperative to understand how myelination impacts disability in MS, as many other factors could contribute to reduced activity and participation. Additionally, as remyelination occurs over 12 to 24 weeks, it is imperative to establish the feasibility of similar duration of aerobic exercise interventions, and explore if exercise independently influences established remyelination outcomes before integration into multimodal strategies. This is a randomized, single-blind, parallel clinical trial of a 24-week aerobic stationary cycling intervention to determine feasibility and explore if aerobic exercise independently promotes remyelination in pwMS.

Multiple Sclerosis, Sclerosis, Demyelinating Diseases, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Autoimmune Diseases, CNS, Exercise

The first 44 participants with spinal cord injury related to multiple sclerosis (MS) will be randomized in a 1:1 ratio to a 24-week aerobic exercise intervention on a stationary ergometer or an MS education control group.

Twenty-two participants in the clinical trial arm will be randomized to MS:Cycle: an aerobic exercise intervention on a stationary ergometer. Participants will exercise thrice weekly for 30 minutes with graded supervision for 24 weeks.

Twenty-two participants in the clinical trial arm will be randomized to MS: Take Control (MSTC): a monthly, hour-long MS education control group led by a trained facilitator.

Aerobic exercise performed on a stationary ergometer for 30 minutes, thrice weekly, with graded supervision. Participants will participate in the intervention over 24 weeks.

A patient reported outcome of fatigue severity with a range of 0-84 (higher scores indicate more fatigue).

A patient reported outcome of pain with a range of 6-30 (higher scores indicate a greater impact of pain on a person's mood or behavior).

A patient reported outcome of MS disability ranging from 0-8 (with higher scores indicating increased disability).

A patient reported outcome of fatigue severity with a range of 0-84 (higher scores indicate more fatigue).

A patient reported outcome of pain with a range of 6-30 (higher scores indicate a greater impact of pain on a person's mood or behavior).

Inclusion Criteria: Physician-confirmed diagnosis of MS based on the 2017 McDonald criteria 18-64 years old Have access to the internet and a device that can access virtual visits (Inclusion criteria to advance to clinical trial) Somatosensory evoked potential (SSEP) latency z-score ≥2 for P40 or inter-side difference in z-score ≥2 for P40 Exclusion Criteria: Medical or biophysical conditions that prohibit the use of a cycle ergometer or treadmill (medical readiness to be assessed by the Activity Readiness Questionnaire (PAR-Q)) or achievement of target heart rate. Engages in >30 minutes/week of aerobic activity regularly. Clinically confirmed MS relapse in the last 3 months. Changes in disease modifying therapy (DMT) for MS in the last 6 months. Pregnant women. Treatment with steroids for MS in the last 30 days. Concurrent use of 4-aminopyridine or dalfampridine (medications which can alter SSEP) and unwilling to discontinue it for 2 days prior to SSEP testing. Have a known history of severe spinal canal stenosis