Aerobic Exercise for Remyelination in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04539002
• Other study ID #: STUDY00021045
• Secondary ID: K23HD101667UL1TR
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 29, 2021
• Est. completion date: March 9, 2026

Study information

• Verified date: April 2023
• Source: Oregon Health and Science University
• Contact: Lindsey B Wooliscroft, MD, MSc, MCR
• Phone: 503-494-5759
• Email: wooliscr[@]ohsu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 9, 2026
• Est. primary completion date: November 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.
• Education Group Control
A monthly, hour-long, class over various MS topics and symptoms, led by a trained facilitator.

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (7)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient Determined Disease Steps (PDDS)	A patient reported outcome of MS disability ranging from 0-8 (with higher scores indicating increased disability).	Baseline
Other	Activity Readiness Questionnaire (PAR-Q)	An assessment of safety to participate in exercise	Baseline and 12 weeks
Other	6-Minute Timed Walk (6MTW)	An assessment of exercise tolerance	From baseline to week 12
Other	Timed Up and Go (TUG)	A test of walking agility	From baseline to week 12
Other	Timed 25-Foot Walk (T25FW)	A test of walking speed	From baseline to week 12
Other	Fall frequency	A self-report of fall frequency over the last 30 days	From baseline to week 12
Other	9 Hole Peg Test	A test of upper extremity and arm function	From baseline to week 12
Other	Multiple Sclerosis Functional Composite (MSFC)	Composite measure of walking speed, upper extremity function and cognition.	From baseline to week 12
Other	Symbol Digit Modalities Test (SDMT)	A test of cognitive function	From baseline to week 12
Other	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
Other	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
Other	Somatosensory Evoked Potentials (SSEPs)	Measure of functional myelination of the somatosensory tracts of the spinal cord	From baseline to week 12
Other	Strength testing	Strength of the quadriceps, hamstrings, and hand grip is measured with dynamometers	From baseline to week 24
Other	Strength testing	Strength of the quadriceps, hamstrings, and hand grip is measured with dynamometers	From baseline to week 12
Other	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
Other	International Physical Activity Questionnaire Short Form (IPAQ-SF)	A patient reported outcome of physical activity	From baseline to week 12
Primary	Somatosensory Evoked Potentials (SSEPs)	Measure of functional myelination of the somatosensory tracts of the spinal cord	From baseline to week 24
Secondary	6-Minute Timed Walk (6MTW)	An assessment of exercise tolerance	From baseline to week 24
Secondary	Timed Up and Go (TUG)	A test of walking agility	From baseline to week 24
Secondary	Timed 25-Foot Walk (T25FW)	A test of walking speed	From baseline to week 24
Secondary	Fall frequency	A self-report of fall frequency over the last 30 days	From baseline to week 24
Secondary	9 Hole Peg Test	A test of upper extremity and arm function	From baseline to week 24
Secondary	Multiple Sclerosis Functional Composite (MSFC)	Composite measure of walking speed, upper extremity function and cognition.	From baseline to week 24
Secondary	Virtual aerobic exercise intervention adherence	Defined as participation in at least 80% of the exercise sessions in the trial	From baseline to week 24
Secondary	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
Secondary	Average heart rate (HR) zone during exercise sessions	Average HR zone during exercise sessions	From baseline to week 24
Secondary	Brain Myelin Water Fraction (MWF)	MWF imaging of the corpus callosum, internal capsules and MS lesions	From baseline to week 24
Secondary	Symbol Digit Modalities Test (SDMT)	A test of cognitive function	From baseline to week 24
Secondary	VO2 max	A test of aerobic fitness	From baseline to week 24
Secondary	7-site skinfold test	A test of body composition	From baseline to week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	International Physical Activity Questionnaire Short Form (IPAQ-SF)	A patient reported outcome of physical activity	From baseline to week 24