Combating Age-related Failure of Myelination in Multiple Sclerosis: An Exploratory Study (MAPMyeMS)

Combating Age-related Failure of Myelination in Multiple Sclerosis: an Exploratory Study

This observational, longitudinal study will examine whether physical activity and other potentially modifiable lifestyle factors are associated with changes in myelin, the protective coating around nerve fibers, in older adults with multiple sclerosis (MS). Participants will undergo magnetic resonance imaging (MRI) scans to measure myelin throughout the central nervous system and will wear wrist-worn activity trackers to assess physical activity over time.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Observation

Detailed Description

The primary aim of this study is to explore clinical variables and potentially modifiable risk factors that are associated with improved myelination (both enhanced remyelination and reduced demyelination) in older adults living with multiple sclerosis. The emphasis here will be on discovery and generation of pilot data to support further definitive longitudinal observational studies, and ultimately, clinical trials on behavioral and/or pharmaceutical interventions to prevent demyelination and promote remyelination in people living with MS.

Participants will be categorized based on whether they meet or exceed the current physical activity guidelines of at least 150 minutes per week of moderate-intensity aerobic physical activity, 75 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination.

At both baseline and 6 months, MRI and clinical assessments will be obtained, and chart review will be performed. Participants will wear a wrist-worn physical activity monitor and answer monthly questionnaires (assessed via REDCap survey) throughout the study period.

Linear regression will be performed to estimate the effect size of various physical activity variables (step count, sedentary time, and time spent in light/moderate/vigorous physical activity, aerobic capacity and overall strength) with 6-month change in myelination.

• Study Type: Observational
• Enrollment (Estimated): 14

Contacts and Locations

• Study Contact: Name: Susan R Robles, BS; Phone Number: 206-598-0501; Email: msstudy@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98133
      • Multiple Sclerosis Center at UW Medical Center - Northwest
      • Contact: Susan R Robles, BS; Phone Number: 206-598-0501; Email: msstudy@uw.edu
      • Principal Investigator: Sarah B Simmons, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will include adults age 50-70 (inclusive) with a diagnosis of multiple sclerosis in the Greater Seattle area.

Description

Inclusion Criteria:

• Diagnosis of multiple sclerosis
• Independent with ambulation (able to walk 500m without aid)
• Disease duration >10 years
• Age 50 to 70 years (inclusive)
• Be able to read, speak, and understand English

Exclusion Criteria:

• Diagnosis of other neurologic disease that would interfere with interpretation such as stroke, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica (NMO), and sarcoidosis.
• Inability to complete study procedures (including obtaining MRI at BMIC and using Fitbit connected to smartphone)
• Currently participating in another clinical trial on remyelination
• Pregnancy. (Pregnancy status will be asked at screening and before each MRI. Pregnancy testing will not be offered as part of this study.)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adults With Multiple Sclerosis; Participants with multiple sclerosis, age 50-70 (inclusive) will undergo quantitative MRI assessments, wearable activity monitoring, and questionnaire-based assessments over the study period.	Other: Observation; No intervention is administered. Participants undergo observational assessments including MRI, wearable activity monitoring, and questionnaires.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative MRI-derived myelin measure	Change in MRI-derived measures of myelin content within the central nervous system. Specifically, the investigators will use macromolecular proton fraction (MPF), a quantitative MRI parameter which describes the magnetization transfer effect and defined as the relative amount of protons bound to biological macromolecules with restricted molecular motion.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total step count	Total step count will measured using wrist-worn activity tracker.	Continuously collected during the 6-month study period
Self-reported physical activity	Physical activity will be measured with the International Physical Activity Questionnaire-Short Form (IPAQ-SF). This questionnaire will ask participants about their moderate and vigorous physical activity and time spent walking, to give a total sum score of Metabolic Equivalent of Task (MET). Higher calculated (MET) scores indicate greater physical activity.	Baseline and monthly for the 6-month study period
Multiple Sclerosis Functional Composite (MSFC)	The MSFC assesses walking function, hand function, and cognitive function and gives a composite score.	baseline and 6 months
Low Contrast Letter Acuity	The LCLA assesses visual function	Baseline and 6 months
Time spent in moderate-to-vigorous physical activity (MVPA)	MVPA will be measured via wrist-worn physical activity monitor	Throughout the 6-month period
Sedentary Time	Sedentary Time will be measured via wrist-worn fitness tracker	Throughout the 6-month period
Self-reported sedentary time	Self-reported sedentary time will be measured with the International Physical Activity Questionnaire-Short Form (IPAQ-SF). This questionnaire will ask participants about their time spent sitting over the past 7 days, as an estimate of sedentary time.	Baseline and monthly throughout the 6-month period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Function	Physical function will be measured using the PROMIS Physical Function-MS 15a. This self-report questionnaire assesses participants' physical functioning and ability to perform everyday activities.	Baseline and 6 months
Diet Quality	Diet will be measured using the Dietary Screener Questionnaire (DSQ), a self-report questionnaire that assesses the frequency of consumption of selected foods and beverages during the previous month to estimate intake of key dietary components, including fruits, vegetables, whole grains, dairy products, fiber, and added sugars. The outcome measure will be the total DSQ-derived diet quality score.	Baseline and monthly for the 6-month study period.
Sleep Quality	Sleep quality will be measured with the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8a, version 1.0. Responses from each item will be summed to form a total raw score ranging from 8-40. Higher scores indicate higher self-reported levels of sleep disturbance.	Baseline and monthly for the 6-month study period.
Stress	Stress will be measured using the Perceived Stress Scale, a 10-item self-report questionnaire that measures the degree to which situations in an individual's life are appraised as stressful during the previous month. Higher scores indicate greater perceived stress. Raw scores range from 0 to 40 and use reverse scoring for some items.	Baseline and monthly for the 6-month study period.
Depressive Symptom Severity	This outcome will be measured using the Patient Health Questionnaire- 8 (PHQ-8), a 8-item self-report measure that assesses the frequency and severity of depressive symptoms experienced during the previous 2 weeks. Higher scores indicate greater depressive symptom burden.	Baseline and monthly for the 6-month study period.
Fatigue Severity	Fatigue will be measured using the Fatigue Severity Scale, a 9-item self-report questionnaire that evaluates the severity of fatigue and its impact on daily activities, work, family, and social functioning. Higher scores indicate greater fatigue severity.	Baseline and monthly for the 6-month study period.
Alcohol Use	This will be measured via the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), a 3-item screening measure that assesses alcohol consumption patterns, including drinking frequency, quantity, and frequency of heavy drinking episodes. Higher scores indicate greater alcohol use and risk for hazardous drinking.	Baseline and monthly for the 6-month study period.
Cannabis Use	This information will be collected through an adapted version of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU), a self-report measure that assesses cannabis use history and patterns, including age of initiation, frequency of use, quantity consumed, and methods of administration.	Baseline and monthly for the 6-month study period.
Tobacco Use	This information will be collected through a self-developed questionnaire detailing self-reported tobacco and nicotine product use, including current use status, frequency of use, duration of use, and product type.	Baseline and monthly for the 6-month study period.
Comorbidity Burden	This information will be collected using a self-reported questionnaire of presence of physician-diagnosed medical and psychiatric comorbid conditions. Comorbidity burden may be summarized as the total number of reported comorbidities.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: University of Washington

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 15, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; multiple sclerosis; remyelination; demyelination
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Behavior; Multiple Sclerosis; Demyelinating Diseases; Motor Activity; Investigative Techniques; Methods; Observation
• Other Study ID Numbers: STUDY00025928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study data may be shared in de-identified form with outside researchers and collaborators as requested and deemed acceptable by study investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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