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Completed

NCT Number: NCT03677440

Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT

Cognitive impairment is highly prevalent, poorly-managed, and disabling in persons with MS and exercise training might represent a promising approach to manage this symptom of the disease. The proposed study aims to examine the effects of 3-months of supervised, progressive (both intensity and duration) treadmill walking exercise training (designed based on pilot work and American College of Sports Medicine guidelines) compared with an active control condition (i.e., stretching-and-toning activities) on cognitive processing speed and functional MRI outcomes in 88 cognitively-impaired persons with MS. This study is critical for providing evidence supporting treadmill walking exercise training as a behavioral approach for managing slowed cognitive processing speed (i.e., the most common MS-related cognitive impairment) and improving brain health in persons with MS.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Cognition Disorders Cognitive Dysfunction Cognitive Impairment Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Mental Disorders Nervous System Diseases Neurocognitive Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Kessler Foundation

West Orange, New Jersey, 07052, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

All participants will:

  • Be between the ages of 18-65
  • Have a clinically definite MS diagnosis based on established criteria
  • Be fully-ambulatory based on Expanded Disability Status Scale (EDSS) scores between 0-4.0
  • Demonstrate slowed CPS based on initial SDMT scores at least 1 SD below the regression-based normative score for healthy controls (i.e., 16th percentile)
  • Be relapse-free and will not have acutely taken corticosteroids for at least 30 days (i.e., relative neurologic stability)
  • Not have a history of major depressive disorder, schizophrenia, bipolar disorder I or II, or substance-abuse disorders.
  • Not be taking medications that can affect cognition (e.g., antipsychotics, benzodiazepines).
  • Be right-handed
  • Have corrected vision better than 20/80
  • Not have known/diagnosed cardiovascular, metabolic, or renal disease. Individuals with known/diagnosed cardiovascular, metabolic, or renal disease who are asymptomatic will be included only with a physician's approval.
  • Demonstrate scores on the Mini-Mental State Examination (MMSE) of 21 or higher (no decisional impairment)
  • Be on a stable disease-modifying therapy regimen (i.e., at least 6 months prior to study enrollment).
  • Have a low risk for contraindications for MRI based on not having metal (e.g., non-MRI compatible aneurysm clips, metal shards in the body or eyes, or recently placed surgical hardware) or electronic devices (e.g., pacemaker, cochlear implant) within the body.
  • Not be pregnant
  • Not be engaging in ≥ 150 min of moderate-to-vigorous physical activity (i.e., not meeting public health guidelines for physical activity) per week
  • Not be actively engaging in cognitive rehabilitation, or participating in regular brain fitness activities
  • Demonstrate systolic blood pressure values of < 200 mmHg or diastolic blood pressure values < 110 mmHg at rest

Treatment and study plan

Treadmill Walking Exercise Training

Behavioral

12-weeks of supervised, progressive treadmill walking exercise training

Stretching-and-Toning Exercise Training

Behavioral

12-weeks of supervised, progressive stretching-and-toning exercise training

Primary outcomes

  1. Cognitive Processing Speed

    Time frame: Baseline, Follow-up (up to 14 weeks)

    Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed)

  2. Thalamocortical Resting-State Functional Connectivity Region 1

    Time frame: Follow-up at 12-weeks minus baseline

    Change in functional connectivity between the thalamus and left superior medial gyrus based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity.

  3. Change in Thalamocortical Resting State Functional Connectivity Region 2

    Time frame: Follow-up at 12-weeks minus baseline

    Resting-state functional connectivity between the thalamus and left putamen based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity.

Secondary outcomes

  1. 3-second Paced Auditory Serial Addition Test (PASAT)

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The 3-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The total score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition

  2. 2-second Paced Auditory Serial Addition Test (PASAT)

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The 2-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The raw score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition.

  3. Pattern Comparison Test

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The Pattern Comparison Test is a neuropsychological test of cognitive processing speed wherein participants are asked to specify whether or not two patterns are the same or different. The primary outcome is the total number of correct answers provided by the participant across two 20-second trials. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognitive processing speed.

  4. Community Integration Questionnaire

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The Community Integration Questionnaire is a patient-reported measure of community participation. The minimum score is 0 and the maximum score is 31, with higher scores reflecting better community participation.

  5. Lawton-Brody Instrumental Activities of Daily Living

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The Lawton-Brody Instrumental Activities of Daily Living is a patient-reported measure of the ability to perform instrumental activities of daily living. The minimum score is 0 and the maximum score is 8, with higher scores reflecting a better ability to complete instrumental activities of daily living.

  6. Multiple Sclerosis Impact Scale-29 Physical Subscale

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The Multiple Sclerosis Impact Scale-29 is a patient-reported measure of the impact of multiple sclerosis on physical and mental domains. In this outcome measure, the physical subscale is the component of interest. The minimum score is 0 and the maximum score is 100, with higher scores reflecting greater impact of MS on physical outcomes.

  7. Timed 25-foot Walk

    Time frame: Baseline, Follow-up (up to 14-weeks)

    The timed 25-foot walk is a neuroperformance outcome where participants are asked to walk as quickly and as safely as possible over a 25-foot course free of debris. The primary outcome is the time to walk 25 feet - averaged across two trials. Higher scores reflect slower walking speed and lower scores reflect faster walking speed.

Sponsors and collaborators

Lead sponsor

Kessler Foundation

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institutes of Health (NIH)

Registry information

Official study title

Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial

Important dates

Study start
2019
Primary completion
2023
Study completion
2024
First posted
Sep 19, 2018
Registry last updated
Jun 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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