Aerobic Exercise for Remyelination in Multiple Sclerosis

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

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

Intervention / Treatment
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* Behavioral: Aerobic exercise
* Behavioral: Education Group Control


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MS: Cycle<br>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. | Behavioral: Aerobic exercise<br>* Aerobic exercise performed on a stationary ergometer for 30 minutes, thrice weekly, with graded supervision. Participants will participate in the intervention over 24 weeks.<br>|
| Active Comparator: MS: Take Control<br>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. | Behavioral: Education Group Control<br>* A monthly, hour-long, class over various MS topics and symptoms, led by a trained facilitator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Somatosensory Evoked Potentials (SSEPs) | Measure of functional myelination of the somatosensory tracts of the spinal cord | From baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-Minute Timed Walk (6MTW) | An assessment of exercise tolerance | From baseline to week 24 | 
| Timed Up and Go (TUG) | A test of walking agility | From baseline to week 24 | 
| Timed 25-Foot Walk (T25FW) | A test of walking speed | From baseline to week 24 | 
| Fall frequency | A self-report of fall frequency over the last 30 days | From baseline to week 24 | 
| 9 Hole Peg Test | A test of upper extremity and arm function | From baseline to week 24 | 
| Multiple Sclerosis Functional Composite (MSFC) | Composite measure of walking speed, upper extremity function and cognition. | From baseline to week 24 | 
| Virtual aerobic exercise intervention adherence | Defined as participation in at least 80% of the exercise sessions in the trial | From baseline to week 24 | 
| Virtual education control group adherence | Defined as participation in at least 80% of the education group sessions in the trial | From baseline to week 24 | 
| Average heart rate (HR) zone during exercise sessions | Average HR zone during exercise sessions | From baseline to week 24 | 
| Brain Myelin Water Fraction (MWF) | MWF imaging of the corpus callosum, internal capsules and MS lesions | From baseline to week 24 | 
| Symbol Digit Modalities Test (SDMT) | A test of cognitive function | From baseline to week 24 | 
| VO2 max | A test of aerobic fitness | From baseline to week 24 | 
| 7-site skinfold test | A test of body composition | From baseline to week 24 | 
| Modified Fatigue Impact Scale (MFIS) | A patient reported outcome of fatigue severity with a range of 0-84 (higher scores indicate more fatigue). | From baseline to week 24 | 
| Pain Effects Scale (PES) | 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). | From baseline to week 24 | 
| Health-related quality of life (QoL) | Neuro-QoL questionnaires of upper and lower extremity function, depression, sleep, and self efficacy | From baseline to weeks 24 | 
| International Physical Activity Questionnaire Short Form (IPAQ-SF) | A patient reported outcome of physical activity | From baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Aerobic Exercise, Remyelination, Neural Repair, Mobility