Clinical trial NCT04539002: Aerobic Exercise for Remyelination in Multiple Sclerosis
Official title: Aerobic Exercise to Improve Mobility in Multiple Sclerosis: Optimizing Design and Execution for a Full-scale Multimodal Remyelination Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Sclerosis
Demyelinating Diseases
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Autoimmune Diseases, CNS
Exercise
Keywords: Exercise
Aerobic Exercise
Remyelination
Neural Repair
Mobility
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Portland VA Medical Center
name: Oregon Clinical and Translational Research Institute
name: Myelin Repair Foundation
name: EMD Serono
name: Medical Research Foundation, Oregon
First posted: 2020-09-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Somatosensory Evoked Potentials (SSEPs)
timeFrame: From baseline to week 24
Secondary outcomes:
measure: 6-Minute Timed Walk (6MTW)
timeFrame: From baseline to week 24
measure: Timed Up and Go (TUG)
timeFrame: From baseline to week 24
measure: Timed 25-Foot Walk (T25FW)
timeFrame: From baseline to week 24
measure: Fall frequency
timeFrame: From baseline to week 24
measure: 9 Hole Peg Test
timeFrame: From baseline to week 24
measure: Multiple Sclerosis Functional Composite (MSFC)
timeFrame: From baseline to week 24
measure: Virtual aerobic exercise intervention adherence
timeFrame: From baseline to week 24
measure: Virtual education control group adherence
timeFrame: From baseline to week 24
measure: Average heart rate (HR) zone during exercise sessions
timeFrame: From baseline to week 24
measure: Brain Myelin Water Fraction (MWF)
timeFrame: From baseline to week 24
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: From baseline to week 24
measure: VO2 max
timeFrame: From baseline to week 24
measure: 7-site skinfold test
timeFrame: From baseline to week 24
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: From baseline to week 24
measure: Pain Effects Scale (PES)
timeFrame: From baseline to week 24
measure: Health-related quality of life (QoL)
timeFrame: From baseline to weeks 24
measure: International Physical Activity Questionnaire Short Form (IPAQ-SF)
timeFrame: From baseline to week 24
Other outcomes:
measure: Patient Determined Disease Steps (PDDS)
timeFrame: Baseline
measure: Activity Readiness Questionnaire (PAR-Q)
timeFrame: Baseline and 12 weeks
measure: 6-Minute Timed Walk (6MTW)
timeFrame: From baseline to week 12
measure: Timed Up and Go (TUG)
timeFrame: From baseline to week 12
measure: Timed 25-Foot Walk (T25FW)
timeFrame: From baseline to week 12
measure: Fall frequency
timeFrame: From baseline to week 12
measure: 9 Hole Peg Test
timeFrame: From baseline to week 12
measure: Multiple Sclerosis Functional Composite (MSFC)
timeFrame: From baseline to week 12
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: From baseline to week 12
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: From baseline to week 12
measure: Pain Effects Scale (PES)
timeFrame: From baseline to week 12
measure: Somatosensory Evoked Potentials (SSEPs)
timeFrame: From baseline to week 12
measure: Strength testing
timeFrame: From baseline to week 24
measure: Strength testing
timeFrame: From baseline to week 12
measure: Health-related quality of life (QoL)
timeFrame: From baseline to weeks 12
measure: International Physical Activity Questionnaire Short Form (IPAQ-SF)
timeFrame: From baseline to week 12
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Lindsey B Wooliscroft, MD
role: PRINCIPAL_INVESTIGATOR
References: