Back to resultsExercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT
Primary Purpose
Multiple Sclerosis, Cognitive Impairment
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Treadmill Walking Exercise Training
Stretching-and-Toning Exercise Training
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
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
Sites / Locations
- Kessler Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Treadmill Walking Exercise Training
Stretching-and-Toning Exercise Training
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Cognitive Processing Speed
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
Functional connectivity between the thalamus and right medial frontal gyrus based on fMRI
Thalamocortical Resting State Functional Connectivity Region 2
Resting-state functional connectivity between the thalamus and anterior cingulate cortex based on fMRI
Secondary Outcome Measures
Full Information
NCT ID
NCT03677440
First Posted
September 14, 2018
Last Updated
September 7, 2023
Sponsor
Kessler Foundation
Collaborators
National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT03677440
Brief Title
Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT
Official Title
Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 5, 2019 (Actual)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
March 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kessler Foundation
Collaborators
National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Cognitive Impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Participants will be unaware if the treadmill walking exercise training or stretching-and-toning conditions represent the experimental or control conditions; outcome assessors will be treatment-blinded; MRI data analysts will be blinded to condition
Allocation
Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treadmill Walking Exercise Training
Arm Type
Experimental
Arm Description
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.
Arm Title
Stretching-and-Toning Exercise Training
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Treadmill Walking Exercise Training
Intervention Description
12-weeks of supervised, progressive treadmill walking exercise training
Intervention Type
Behavioral
Intervention Name(s)
Stretching-and-Toning Exercise Training
Intervention Description
12-weeks of supervised, progressive stretching-and-toning exercise training
Primary Outcome Measure Information:
Title
Cognitive Processing Speed
Description
Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed)
Time Frame
Every 12 weeks
Title
Thalamocortical Resting-State Functional Connectivity Region 1
Description
Functional connectivity between the thalamus and right medial frontal gyrus based on fMRI
Time Frame
Every 12 weeks
Title
Thalamocortical Resting State Functional Connectivity Region 2
Description
Resting-state functional connectivity between the thalamus and anterior cingulate cortex based on fMRI
Time Frame
Every 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian M Sandroff, PhD
Organizational Affiliation
Kessler Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kessler Foundation
City
West Orange
State/Province
New Jersey
ZIP/Postal Code
07052
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT
We'll reach out to this number within 24 hrs