Trial Outcomes & Findings for Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT (NCT NCT03677440)

Last Updated: 2025-06-05

Results Overview

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

Recruitment status

COMPLETED

Study phase

Target enrollment

43 participants

Primary outcome timeframe

Baseline, Follow-up (up to 14 weeks)

Results posted on

2025-06-05

Participant Flow

N=4 participants who were enrolled into the study subsequently dropped out prior to random assignment. Thus, 43 participants were enrolled into the study and 39 participants were randomly assigned into the study arms.

Participant milestones

Participant milestones
Measure	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. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training	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. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training
Overall Study STARTED	19	20
Overall Study COMPLETED	13	15
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treadmill Walking Exercise Training n=18 Participants 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. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training	Stretching-and-Toning Exercise Training n=19 Participants 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. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training	Total n=37 Participants Total of all reporting groups
Age, Continuous	44.5 Years STANDARD_DEVIATION 8.0 • n=5 Participants	46.1 Years STANDARD_DEVIATION 11.2 • n=7 Participants	45.3 Years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Education	16.1 Years STANDARD_DEVIATION 2.5 • n=5 Participants	15.2 Years STANDARD_DEVIATION 2.2 • n=7 Participants	15.6 Years STANDARD_DEVIATION 2.4 • n=5 Participants
Expanded Disability Status Scale	3.0 units on a scale n=5 Participants	3.5 units on a scale n=7 Participants	3.5 units on a scale n=5 Participants
Disease Duration	13.9 years STANDARD_DEVIATION 9.9 • n=5 Participants	10.9 years STANDARD_DEVIATION 7.4 • n=7 Participants	11.8 years STANDARD_DEVIATION 8.5 • n=5 Participants
MS Phenotype Relapsing-Remitting	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
MS Phenotype Progressive	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
MS Phenotype Unknown	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Symbol Digit Modalities Test z-score	-2.0 z-score STANDARD_DEVIATION 0.7 • n=5 Participants	-1.9 z-score STANDARD_DEVIATION 0.6 • n=7 Participants	-1.9 z-score STANDARD_DEVIATION 0.6 • n=5 Participants

PRIMARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Treadmill Walking Exercise Training n=13 Participants 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. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training	Stretching-and-Toning Exercise Training n=15 Participants 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. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training
Cognitive Processing Speed Baseline	43.5 Raw Score Standard Deviation 9.6	43.7 Raw Score Standard Deviation 9.2
Cognitive Processing Speed Follow-up	46.5 Raw Score Standard Deviation 12.1	49.1 Raw Score Standard Deviation 10.7

PRIMARY outcome

Timeframe: Follow-up at 12-weeks minus baseline

Population: N=3 participants did not complete MRI at follow-up (12-weeks)

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.

Outcome measures

Outcome measures
Measure	Treadmill Walking Exercise Training n=11 Participants 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. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training	Stretching-and-Toning Exercise Training n=14 Participants 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. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training
Thalamocortical Resting-State Functional Connectivity Region 1	.0334 z-score Standard Deviation .0531	-.0247 z-score Standard Deviation .0605

PRIMARY outcome

Timeframe: Follow-up at 12-weeks minus baseline

Population: N=3 participants did not complete MRI at follow-up (12-weeks)

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.