Trial results for Project EXACT, investigating exercise training effects on cognition and brain function in Multiple Sclerosis, were posted on ClinicalTrials.gov on 2025-06-05. The study found that treadmill walking exercise significantly improved thalamocortical resting-state functional connectivity in patients with Multiple Sclerosis and cognitive impairment, with p-values of 0.01 and 0.02 for two distinct regions.
Background
Cognitive impairment is a common, often poorly managed, and disabling symptom in individuals with Multiple Sclerosis. Exercise training has been explored as a potential strategy to manage this aspect of the disease, aiming to improve cognitive function and associated brain activity.
Trial design
This completed study enrolled 43 participants and investigated conditions including Multiple Sclerosis and Cognitive Impairment. The trial compared 3-months of supervised, progressive treadmill walking exercise training against an active control condition of stretching-and-toning activities. The study aimed to examine the effects of these interventions on cognitive processing speed and functional MRI outcomes.
Key results
The study reported on several key measurements:
- Cognitive Processing Speed:
- For the Treadmill Walking Exercise Training group, the mean raw score was 43.5 (Standard Deviation 9.6) at one time point and 46.5 (Standard Deviation 12.1) at another.
- For the Stretching-and-Toning Exercise Training group, the mean raw score was 43.7 (Standard Deviation 9.2) at one time point and 49.1 (Standard Deviation 10.7) at another.
- Thalamocortical Resting-State Functional Connectivity Region 1:
- The Treadmill Walking Exercise Training group showed a mean z-score of 0.0334 (Standard Deviation 0.0531).
- The Stretching-and-Toning Exercise Training group showed a mean z-score of -0.0247 (Standard Deviation 0.0605).
- Change in Thalamocortical Resting State Functional Connectivity Region 2:
- The Treadmill Walking Exercise Training group showed a mean z-score of 0.0193 (Standard Deviation 0.0595).
- The Stretching-and-Toning Exercise Training group showed a mean z-score of -0.0414 (Standard Deviation 0.0783).
- 3-second Paced Auditory Serial Addition Test (PASAT):
- For the Treadmill Walking Exercise Training group, the mean score on a scale was 33.8 (Standard Deviation 16) at one time point and 35.9 (Standard Deviation 17.0) at another.
- For the Stretching-and-Toning Exercise Training group, the mean score on a scale was 34 (Standard Deviation 13.4) at one time point and 37.4 (Standard Deviation 13.7) at another.
Key analyses revealed:
- A repeated-measures ANOVA testing a condition-by-time interaction on Symbol Digit Modalities Test scores (related to cognitive processing speed) yielded a p-value of 0.34, indicating no statistically significant difference between groups.
- A 1-sided t-test for Thalamocortical Resting-State Functional Connectivity Region 1 showed a p-value of 0.01.
- A 1-sided t-test for Change in Thalamocortical Resting State Functional Connectivity Region 2 showed a p-value of 0.02.
- An ANOVA for PASAT scores yielded a p-value of 0.63, indicating no statistically significant difference between groups.
What this means
The statistically significant findings for thalamocortical resting-state functional connectivity suggest that treadmill walking exercise training may positively influence brain connectivity in individuals with Multiple Sclerosis and cognitive impairment. While cognitive processing speed, as measured by the Symbol Digit Modalities Test and PASAT, did not show statistically significant improvements between the exercise and control groups, the observed changes in brain connectivity warrant further investigation into the potential neurobiological benefits of exercise in this patient population.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT03677440, titled "Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT", were posted on 2025-06-05 on clinicaltrials.gov.