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Aerobic Exercise for Remyelination in Multiple Sclerosis

Phase 1
Active, not recruiting
Conditions
Multiple Sclerosis
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Autoimmune Diseases, CNS
Sclerosis
Demyelinating Diseases
Exercise
Interventions
Behavioral: Education Group Control
Behavioral: Aerobic exercise
Registration Number
NCT04539002
Lead Sponsor
Oregon Health and Science University
Brief Summary

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

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MS: Take ControlEducation Group ControlTwenty-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.
MS: CycleAerobic exerciseTwenty-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.
Primary Outcome Measures
NameTimeMethod
Somatosensory Evoked Potentials (SSEPs)From baseline to week 24

Measure of functional myelination of the somatosensory tracts of the spinal cord

Secondary Outcome Measures
NameTimeMethod
9 Hole Peg TestFrom baseline to week 24

A test of upper extremity and arm function

Timed 25-Foot Walk (T25FW)From baseline to week 24

A test of walking speed

Virtual aerobic exercise intervention adherenceFrom baseline to week 24

Defined as participation in at least 80% of the exercise sessions in the trial

VO2 maxFrom baseline to week 24

A test of aerobic fitness

7-site skinfold testFrom baseline to week 24

A test of body composition

Fall frequencyFrom baseline to week 24

A self-report of fall frequency over the last 30 days

Multiple Sclerosis Functional Composite (MSFC)From baseline to week 24

Composite measure of walking speed, upper extremity function and cognition.

Average heart rate (HR) zone during exercise sessionsFrom baseline to week 24

Average HR zone during exercise sessions

Brain Myelin Water Fraction (MWF)From baseline to week 24

MWF imaging of the corpus callosum, internal capsules and MS lesions

6-Minute Timed Walk (6MTW)From baseline to week 24

An assessment of exercise tolerance

Timed Up and Go (TUG)From baseline to week 24

A test of walking agility

Virtual education control group adherenceFrom baseline to week 24

Defined as participation in at least 80% of the education group sessions in the trial

Symbol Digit Modalities Test (SDMT)From baseline to week 24

A test of cognitive function

Health-related quality of life (QoL)From baseline to weeks 24

Neuro-QoL questionnaires of upper and lower extremity function, depression, sleep, and self efficacy

Modified Fatigue Impact Scale (MFIS)From baseline to week 24

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

Pain Effects Scale (PES)From baseline to week 24

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).

International Physical Activity Questionnaire Short Form (IPAQ-SF)From baseline to week 24

A patient reported outcome of physical activity

Trial Locations

Locations (1)

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

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