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

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).

Study Overview

• Status: Recruiting
• Conditions: Nervous System Diseases; Multiple Sclerosis; Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Exercise
• Intervention / Treatment: Behavioral: Aerobic exercise; Behavioral: Education Group Control

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lindsey B Wooliscroft, MD, MSc, MCR; Phone Number: 503-494-5759; Email: wooliscr@ohsu.edu
• Study Contact Backup: Name: Michelle Cameron, MD, PT, MCR; Phone Number: 503-494-5759; Email: cameromi@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Lindsey Wooliscroft, MD, MS; Phone Number: 503-494-5759; Email: wooliscr@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Determined Disease Steps (PDDS)	A patient reported outcome of MS disability ranging from 0-8 (with higher scores indicating increased disability).	Baseline
Activity Readiness Questionnaire (PAR-Q)	An assessment of safety to participate in exercise	Baseline and 12 weeks
6-Minute Timed Walk (6MTW)	An assessment of exercise tolerance	From baseline to week 12
Timed Up and Go (TUG)	A test of walking agility	From baseline to week 12
Timed 25-Foot Walk (T25FW)	A test of walking speed	From baseline to week 12
Fall frequency	A self-report of fall frequency over the last 30 days	From baseline to week 12
9 Hole Peg Test	A test of upper extremity and arm function	From baseline to week 12
Multiple Sclerosis Functional Composite (MSFC)	Composite measure of walking speed, upper extremity function and cognition.	From baseline to week 12
Symbol Digit Modalities Test (SDMT)	A test of cognitive function	From baseline to week 12
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 12
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 12
Somatosensory Evoked Potentials (SSEPs)	Measure of functional myelination of the somatosensory tracts of the spinal cord	From baseline to week 12
Strength testing	Strength of the quadriceps, hamstrings, and hand grip is measured with dynamometers	From baseline to week 24
Strength testing	Strength of the quadriceps, hamstrings, and hand grip is measured with dynamometers	From baseline to week 12
Health-related quality of life (QoL)	Neuro-QoL questionnaires of upper and lower extremity function, depression, sleep, and self efficacy	From baseline to weeks 12
International Physical Activity Questionnaire Short Form (IPAQ-SF)	A patient reported outcome of physical activity	From baseline to week 12

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); EMD Serono; Oregon Clinical and Translational Research Institute; Portland VA Medical Center; Medical Research Foundation, Oregon; Myelin Repair Foundation
• Investigators: Principal Investigator: Lindsey B Wooliscroft, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Anticipated): November 3, 2025
• Study Completion (Anticipated): March 9, 2026

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 31, 2020
• First Posted (Actual): September 4, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Aerobic Exercise; Mobility; Remyelination; Neural Repair
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Immune System Diseases; Leukoencephalopathies; Multiple Sclerosis; Sclerosis; Nervous System Diseases; Autoimmune Diseases; Demyelinating Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Autoimmune Diseases, CNS
• Other Study ID Numbers: STUDY00021045; K23HD101667 (U.S. NIH Grant/Contract); UL1TR002369 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No