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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis; Cognitive Impairment
• Intervention / Treatment: Behavioral: Treadmill Walking Exercise Training; Behavioral: Stretching-and-Toning Exercise Training

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brian M Sandroff, PhD; Phone Number: 973-965-6649; Email: bsandroff@kesslerfoundation.org

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Processing Speed	Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed)	Every 12 weeks
Thalamocortical Resting-State Functional Connectivity Region 1	Functional connectivity between the thalamus and right medial frontal gyrus based on fMRI	Every 12 weeks
Thalamocortical Resting State Functional Connectivity Region 2	Resting-state functional connectivity between the thalamus and anterior cingulate cortex based on fMRI	Every 12 weeks

Collaborators and Investigators

• Sponsor: Kessler Foundation
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Brian M Sandroff, PhD, Kessler Foundation

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2019
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (Actual): September 19, 2018

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: IRB-300000111; 1R01HD091155-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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