Autoimmune Diseases of the Nervous System, Demyelinating Autoimmune Diseases, CNS, Demyelinating Diseases, Exercise, Multiple Sclerosis, Nervous System Diseases, Sclerosis
Conditions
Keywords
Exercise, Aerobic Exercise, Remyelination, Neural Repair, Mobility
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.
Interventions
BEHAVIORALAerobic 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.
BEHAVIORALEducation Group Control
A monthly, hour-long, class over various MS topics and symptoms, led by a trained facilitator.
Sponsors
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
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Single-blind, randomized, controlled
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Somatosensory Evoked Potentials (SSEPs) | From baseline to week 24 | Measure of functional myelination of the somatosensory tracts of the spinal cord |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Timed Up and Go (TUG) | From baseline to week 24 | A test of walking agility |
| Timed 25-Foot Walk (T25FW) | From baseline to week 24 | A test of walking speed |
| Fall frequency | From baseline to week 24 | A self-report of fall frequency over the last 30 days |
| 9 Hole Peg Test | From baseline to week 24 | A test of upper extremity and arm function |
| Multiple Sclerosis Functional Composite (MSFC) | From baseline to week 24 | Composite measure of walking speed, upper extremity function and cognition. |
| Virtual aerobic exercise intervention adherence | From baseline to week 24 | Defined as participation in at least 80% of the exercise sessions in the trial |
| Virtual education control group adherence | From baseline to week 24 | Defined as participation in at least 80% of the education group sessions in the trial |
| Average heart rate (HR) zone during exercise sessions | From 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 |
| Symbol Digit Modalities Test (SDMT) | From baseline to week 24 | A test of cognitive function |
| VO2 max | From baseline to week 24 | A test of aerobic fitness |
| 7-site skinfold test | From baseline to week 24 | A test of body composition |
| 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). |
| 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 |
| International Physical Activity Questionnaire Short Form (IPAQ-SF) | From baseline to week 24 | A patient reported outcome of physical activity |
| 6-Minute Timed Walk (6MTW) | From baseline to week 24 | An assessment of exercise tolerance |
Other
| Measure | Time frame | Description |
|---|---|---|
| Activity Readiness Questionnaire (PAR-Q) | Baseline and 12 weeks | An assessment of safety to participate in exercise |
| Timed Up and Go (TUG) | From baseline to week 12 | A test of walking agility |
| Timed 25-Foot Walk (T25FW) | From baseline to week 12 | A test of walking speed |
| Fall frequency | From baseline to week 12 | A self-report of fall frequency over the last 30 days |
| 9 Hole Peg Test | From baseline to week 12 | A test of upper extremity and arm function |
| Multiple Sclerosis Functional Composite (MSFC) | From baseline to week 12 | Composite measure of walking speed, upper extremity function and cognition. |
| Symbol Digit Modalities Test (SDMT) | From baseline to week 12 | A test of cognitive function |
| Modified Fatigue Impact Scale (MFIS) | From baseline to week 12 | 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 12 | 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). |
| Somatosensory Evoked Potentials (SSEPs) | From baseline to week 12 | Measure of functional myelination of the somatosensory tracts of the spinal cord |
| Strength testing | From baseline to week 24 | Strength of the quadriceps, hamstrings, and hand grip is measured with dynamometers |
| Health-related quality of life (QoL) | From baseline to weeks 12 | Neuro-QoL questionnaires of upper and lower extremity function, depression, sleep, and self efficacy |
| International Physical Activity Questionnaire Short Form (IPAQ-SF) | From baseline to week 12 | A patient reported outcome of physical activity |
| Patient Determined Disease Steps (PDDS) | Baseline | A patient reported outcome of MS disability ranging from 0-8 (with higher scores indicating increased disability). |
| 6-Minute Timed Walk (6MTW) | From baseline to week 12 | An assessment of exercise tolerance |
Countries
United States
Outcome results
None listed