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

Sponsor

Kessler Foundation (Other)

Overall Status

Recruiting

CT.gov ID

NCT03677440

Collaborator

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

Enrollment

Location

Arms

55.8

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Cognitive Impairment	Behavioral: Treadmill Walking Exercise Training Behavioral: Stretching-and-Toning Exercise Training	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes 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

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 5, 2019

Anticipated Primary Completion Date :

Mar 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treadmill Walking Exercise Training 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.	Behavioral: Treadmill Walking Exercise Training 12-weeks of supervised, progressive treadmill walking exercise training
Active Comparator: Stretching-and-Toning Exercise Training 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.	Behavioral: Stretching-and-Toning Exercise Training 12-weeks of supervised, progressive stretching-and-toning exercise training

Arm

Intervention/Treatment

Experimental: Treadmill Walking Exercise Training

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.

Behavioral: Treadmill Walking Exercise Training

12-weeks of supervised, progressive treadmill walking exercise training

Active Comparator: Stretching-and-Toning Exercise Training

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.

Behavioral: Stretching-and-Toning Exercise Training

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

Outcome Measures

Primary Outcome Measures

Cognitive Processing Speed [Every 12 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 [Every 12 weeks]
Functional connectivity between the thalamus and right medial frontal gyrus based on fMRI
Thalamocortical Resting State Functional Connectivity Region 2 [Every 12 weeks]
Resting-state functional connectivity between the thalamus and anterior cingulate cortex based on fMRI

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kessler Foundation	West Orange	New Jersey	United States	07052

Sponsors and Collaborators

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

Investigators

Principal Investigator: Brian M Sandroff, PhD, Kessler Foundation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Brian Sandroff, Principal Investigator, Kessler Foundation

ClinicalTrials.gov Identifier:

NCT03677440

Other Study ID Numbers:

IRB-300000111
1R01HD091155-01A1

First Posted:

Sep 19, 2018

Last Update Posted:

Oct 5, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Multiple Sclerosis

Sclerosis

Study Results

No Results Posted as of Oct 5, 2021