Multiple SclerosisNCT03677440
Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT
A study testing Treadmill Walking Exercise Training and Stretching-and-Toning Exercise Training in people with Multiple Sclerosis and Cognitive Impairment, run by Kessler Foundation at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Cognitive Impairment
- What is being tested?
- Treadmill Walking Exercise Training and Stretching-and-Toning Exercise Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2019to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial
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.
- Conditions
- Multiple Sclerosis, Cognitive Impairment
- Being tested
- Treadmill Walking Exercise Training, Stretching-and-Toning Exercise Training
- Medical subject headings
- Multiple Sclerosis, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treadmill Walking Exercise TrainingBehavioural
12-weeks of supervised, progressive treadmill walking exercise training
Stretching-and-Toning Exercise TrainingBehavioural
12-weeks of supervised, progressive stretching-and-toning exercise training
| Study group | Role | What they receive |
|---|---|---|
| Treadmill Walking Exercise Training | Experimental | This condition will include 3-months of supervised, progressive light, moderate, and vigorous intensity treadmill walking exercise training based on ACSM guidelines for maximizing adaptations with exercise training. Exercise intensities will be prescribed based on percent oxygen consumption reserve (% VO2R) using values derived from the baseline graded exercise test.
The exercise training itself will be led by trained exercise leaders who are not involved in the collection of outcome assessments. At the outset of each session, participants will be fitted with a Polar HR Monitor (Oy, Finland), and HR will be monitored continuously throughout each session. Each session will begin with a 5-10 min warm-up, followed by the exercise; the target heart rate reserve (HRR) range associated with the VO2R range will be maintained for as long as possible during each exercise period. This will be followed by a 5-10 min cool-down. Receives: Behavioral: Treadmill Walking Exercise Training |
| Stretching-and-Toning Exercise Training | Active comparator | The active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. Receives: Behavioral: Stretching-and-Toning Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Processing Speed
Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed)
Measured: Baseline, Follow-up (up to 14 weeks)
Thalamocortical Resting-State Functional Connectivity Region 1
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.
Measured: Follow-up at 12-weeks minus baseline
Change in Thalamocortical Resting State Functional Connectivity Region 2
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.
Measured: Follow-up at 12-weeks minus baseline
Secondary outcomes (7)
3-second Paced Auditory Serial Addition Test (PASAT)
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
Measured: Baseline, Follow-up (up to 14-weeks)
2-second Paced Auditory Serial Addition Test (PASAT)
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.
Measured: Baseline, Follow-up (up to 14-weeks)
Pattern Comparison Test
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.
Measured: Baseline, Follow-up (up to 14-weeks)
Community Integration Questionnaire
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.
Measured: Baseline, Follow-up (up to 14-weeks)
Lawton-Brody Instrumental Activities of Daily Living
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.
Measured: Baseline, Follow-up (up to 14-weeks)
Multiple Sclerosis Impact Scale-29 Physical Subscale
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.
Measured: Baseline, Follow-up (up to 14-weeks)
Timed 25-foot Walk
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.
Measured: Baseline, Follow-up (up to 14-weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start5 Feb 2019
- Primary completion31 Dec 2023
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kessler Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Brian Sandroff, Kessler Foundation
- Investigators
- Brian M Sandroff, PhD, Principal investigator, Kessler Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03677440
- Sponsor's protocol ID
- IRB-300000111
- Other IDs
- 1R01HD091155-01A1
- Status last verified
- May 2025
- First submitted
- 14 Sep 2018
- Last updated
- 5 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03677440
- Acronym / sponsor ID
- IRB-300000111
- Conditions
- Multiple Sclerosis, Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Kessler FoundationUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 5 Feb 2019 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 19 Sep 2018 (actual)
- Results
- Posted 5 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treadmill Walking Exercise Training | Experimental | Behavioral: Treadmill Walking Exercise TrainingThis condition will include 3-months of supervised, progressive light, moderate, and vigorous intensity treadmill walking exercise training based on ACSM guidelines for maximizing adaptations with exercise training. Exercise intensities will be prescribed based on percent oxygen consumption reserve (% VO2R) using values derived from the baseline graded exercise test. The exercise training itself will be led by trained exercise leaders who are not involved in the collection of outcome assessments. At the outset of each session, participants will be fitted with a Polar HR Monitor (Oy, Finland), and HR will be monitored continuously throughout each session. Each session will begin with a 5-10 min warm-up, followed by the exercise; the target heart rate reserve (HRR) range associated with the VO2R range will be maintained for as long as possible during each exercise period. This will be followed by a 5-10 min cool-down. |
| Stretching-and-Toning Exercise Training | Active comparator | Behavioral: Stretching-and-Toning Exercise TrainingThe active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treadmill Walking Exercise Training12-weeks of supervised, progressive treadmill walking exercise training | Behavioural | Treadmill Walking Exercise Training |
| Stretching-and-Toning Exercise Training12-weeks of supervised, progressive stretching-and-toning exercise training | Behavioural | Stretching-and-Toning Exercise Training |
Primary outcome
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)
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.
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.
7 secondary outcomes
3-second Paced Auditory Serial Addition Test (PASAT)
Time frame: Baseline, Follow-up (up to 14-weeks)
2-second Paced Auditory Serial Addition Test (PASAT)
Time frame: Baseline, Follow-up (up to 14-weeks)
Pattern Comparison Test
Time frame: Baseline, Follow-up (up to 14-weeks)
Community Integration Questionnaire
Time frame: Baseline, Follow-up (up to 14-weeks)
Lawton-Brody Instrumental Activities of Daily Living
Time frame: Baseline, Follow-up (up to 14-weeks)
Multiple Sclerosis Impact Scale-29 Physical Subscale
Time frame: Baseline, Follow-up (up to 14-weeks)
Timed 25-foot Walk
Time frame: Baseline, Follow-up (up to 14-weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Multiple Sclerosis
RecruitingPhase 1
A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders
B-cell Mediated Autoimmune Disorders
RecruitingPhase 2
A Study to Evaluate the Efficacy, Safety and Tolerability of BMS-986368 in Participants With Multiple Sclerosis Spasticity
Multiple Sclerosis Spasticity
RecruitingPhase 3
A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis
Multiple Sclerosis (MS) Primary Progressive
Active, not recruiting
Tai Chi Training for Persons With Multiple Sclerosis.
Multiple Sclerosis (MS) - Relapsing-remitting
RecruitingPhase 3
A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian M Sandroff, PhD principal investigator
Kessler Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Treadmill Walking Exercise Training and Stretching-and-Toning Exercise Training in people with Multiple Sclerosis and Cognitive Impairment, run by Kessler Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Processing Speed (time frame: Baseline, Follow-up (up to 14 weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025.