Acute Effects of Walking Exercise on Brain Functioning in Multiple Sclerosis (PRIMERS)

The project will involve a within-subjects, repeated-measures research design. Participants will initially be screened for relevant inclusion/exclusion criteria for maximizing safety of participating in an exercise study. If a participant meets those inclusion/exclusion criteria, they will visit Kessler Foundation three times. The first visit will involve a baseline session where participants will complete several cognitive tests. This will be followed by a training session, where participants will be provided with a FitBit, and will be trained by research staff to walk at a rate of 100 steps per minute. Once participants demonstrate proficiency at walking at this rate using the FitBit, participants will complete several questionnaires, followed by a maximal, graded exercise test to determine cardiorespiratory fitness. One week later, participants will return to Kessler Foundation to complete 1 of 2 experimental sessions that will be delivered in a random order that further will be counterbalanced across participants (to minimize the potential effects of session order on brain function and blood flow, respectively). Both experimental sessions will follow the same structure. First, participants will undertake a 30-minute MRI scan at Kessler Foundation to measure brain function and brain blood flow. Immediately following the MRI scan, participants will engage in either 20 minutes of treadmill walking exercise or 20 minutes of overground walking exercise at a rate of 100 steps per minute. Immediately following the 20-minute exercise bouts, participants will undertake another MRI scan for measuring brain function and brain blood flow. Participants will return to Kessler Foundation a third time to complete the opposite experimental session that was not completed during the second visit (i.e., overground walking exercise if treadmill walking exercise was completed during the second visit). In total, each participant will undergo four MRI scans over the course of the study (i.e., pre-treadmill, post-treadmill, pre-overground, post-overground). .

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Behavioral: Moderate intensity walking exercise

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Kessler Foundation

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Clinically-definite MS diagnosis
• Relapse-free for at least 30 days
• Low risk for contraindications for exercise testing
• Low risk for contraindications for MRI
• Historically physically inactive prior to MS diagnosis
• Historically highly physically active prior to MS diagnosis

Exclusion Criteria:

• Diagnosis of uncontrolled major depressive disorder, schizophrenia, bipolar disorder I or II, or substance use disorders
• Taking medications that can affect cognition (e.g., antipsychotics, benzodiazepines)
• Historically moderately physically active prior to MS diagnosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Over ground walking exercise; Participants will walk around a square hallway at a step rate of ~100 steps per minute for 20 minutes while wearing a Fitbit around the waist for measuring steps.	Behavioral: Moderate intensity walking exercise; For each intervention arm, participants will be walking at a moderate intensity, determined based on a step rate of approximately 100 steps per minute (measured by a Fitbit)
Experimental: Treadmill walking exercise; Participants will walk on a motor-driven treadmill at a step rate of ~100 steps per minute for 20 minutes while wearing a Fitbit around the waist for measuring steps.	Behavioral: Moderate intensity walking exercise; For each intervention arm, participants will be walking at a moderate intensity, determined based on a step rate of approximately 100 steps per minute (measured by a Fitbit)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Function	MRI-measured resting-state functional connectivity of the thalamus with other areas of the brain	Weeks 2 and 3
Brain Blood Flow	MRI-measured cerebral blood flow perfusion in the left and right hemispheres	Weeks 2 and 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aerobic fitness	Cardiorespiratory fitness (i.e., peak oxygen consumption (VO2peak)) based on a maximal graded exercise test on a motor-driven treadmill	Week 1
Average steps per day	Free-living physical activity based on average steps per day measured by an ActiGraph accelerometer for a 7-day period	Week 1
Cognitive processing speed	Performance on the Symbol Digit Modalities Test (raw score). Higher scores are indicative of faster cognitive processing speed	Week 1
Aerobic fitness	Cardiorespiratory fitness (i.e., time to exhaustion) based on a maximal graded exercise test on a motor-driven treadmill	Week 1
Verbal learning and memory	Performance on the California Verbal Learning Test II (raw score). Higher scores are indicative of better learning and memory	Week 1
Visuospatial learning and memory	Performance on the Brief Visuospatial Memory Test-Revised (raw score). Higher scores are indicative of better visuospatial learning and memory	Week 1
Time spent in moderate-to-vigorous physical activity	Free-living physical activity based on time spent in moderate-to-vigorous activity measured by an ActiGraph accelerometer for a 7-day period	Week 1

Collaborators and Investigators

• Sponsor: Kessler Foundation

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): February 28, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: January 22, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: MRI; exercise; walking
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Behavior; Multiple Sclerosis; Motor Activity
• Other Study ID Numbers: R-1234-23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will share de-identified IPD upon request for inclusion in potential meta-analyses

Drug and device information, study documents

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