Cognitive-motor Telerehabilitation in MS

Study Overview
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Brief Summary
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The primary goal of this project is providing evidence that a home-based combined cognitive-motor training program improves cognition in persons with multiple sclerosis (MS), compared to single cognitive and motor rehabilitation. Secondary goals are to assess the effects on walking performance and to identify the mechanisms of improvement and predictors of treatment response. The main backbone of this project will be a randomized controlled two-centre clinical trial, in which an at-home computerised cognitive-motor rehabilitation program using telemedicine aimed at improving working memory in persons with MS will be evaluated. Based on the information gathered during this trial, possible mechanisms of improvement will be identified by analysing anatomical and neurophysiological changes on structural MRI and resting-state and task-related EEG before and after rehabilitation. Furthermore, factors that can predict treatment response to the rehabilitation program will be identified.

Official Title
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Cognitive-motor Telerehabilitation in Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Behavioral: Cognitive training
* Behavioral: Motor training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically definite multiple sclerosis (revised McDonald criteria 2017) Expanded Disability Status Scale (EDSS) below 6.0 Digit span backwards z-score between [-3 and -0.5] standard deviations below the median of the normative values Age between 18 and 65 Able to safely perform motor rehabilitation in the home situation (assessed by rehabilitation physician and/or occupational or physiotherapist) Exclusion Criteria: Cognitive rehabilitation within six months before inclusion Inpatient multidisciplinary rehabilitation program within three months before inclusion or planned inpatient program during trial Start of or switch in immunomodulator treatment within three months before inclusion Less than one month post-exacerbation Major psychiatric or medical disorder that could influence cognitive functions Combined vision with optimal correction below 0.6 on Snellen Visual Acuity Test Unable or unwilling to undergo EEG or MRI Refusing informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly assigned to either the cognitive-motor, the cognitive or the motor telerehabilitation group, stratified by baseline activity level and cognition.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive-motor training group<br> | Behavioral: Cognitive training<br>* For the cognitive treatment intervention the widely used cognitive training program RehaCom will be used. This is a computer-aided program with more than 30 modules focusing on different domains of cognition. RehaCom has shown improvements in verbal learning, visuospatial memory, information processing speed, attention, executive functions, depression, fatigue and quality of life in PwMS (PMID 31927200, 28116167, 19825502, 23192417). Patients will train on their home computer without direct therapist supervision, using three RehaCom modules that are focused on improving working memory. Both patients in the combined intervention and the cognitive intervention group will be doing a 45-minute computer session respectively one and two days per week for a total of 12 weeks.<br>* Other names: BrainStim;Behavioral: Motor training<br>* For the motor treatment intervention a patient-tailored aerobic training program will be used. Based on their baseline physical activity level patients can choose out of a number of aerobic activities of either mild, moderate or strenuous intensity, with a total training time of 90 minutes for the motor intervention group and 45 minutes for the combined intervention group, divided over at least two training sessions per week of at least 15 minutes per session. The training will be carried out individually at home, without therapist supervision. All physical activities will be logged using the sport watch equipped with a heart rate sensor and an accelerometer. Training intensity will be assessed using the patient's heart rate and the Rating of Perceived Exertion scale.<br>|
| Active Comparator: Cognitive training group<br> | Behavioral: Cognitive training<br>* For the cognitive treatment intervention the widely used cognitive training program RehaCom will be used. This is a computer-aided program with more than 30 modules focusing on different domains of cognition. RehaCom has shown improvements in verbal learning, visuospatial memory, information processing speed, attention, executive functions, depression, fatigue and quality of life in PwMS (PMID 31927200, 28116167, 19825502, 23192417). Patients will train on their home computer without direct therapist supervision, using three RehaCom modules that are focused on improving working memory. Both patients in the combined intervention and the cognitive intervention group will be doing a 45-minute computer session respectively one and two days per week for a total of 12 weeks.<br>* Other names: BrainStim;|
| Active Comparator: Motor training group<br> | Behavioral: Motor training<br>* For the motor treatment intervention a patient-tailored aerobic training program will be used. Based on their baseline physical activity level patients can choose out of a number of aerobic activities of either mild, moderate or strenuous intensity, with a total training time of 90 minutes for the motor intervention group and 45 minutes for the combined intervention group, divided over at least two training sessions per week of at least 15 minutes per session. The training will be carried out individually at home, without therapist supervision. All physical activities will be logged using the sport watch equipped with a heart rate sensor and an accelerometer. Training intensity will be assessed using the patient's heart rate and the Rating of Perceived Exertion scale.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Digit span backwards | Measure of working memory | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) | Measure of cognition in MS | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 
| Change in Corsi backwards | Measure of working memory | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 
| Change in Expanded Disability Status Scale (EDSS) | Measure of disability in MS | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 
| Change in 6-Minute Walk Test (6MWT) | Measure of walking performance | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 
| Change in 25-Foot Walk Test (25FWT) | Measure of walking performance | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 
| Change in 9-Hole Peg Test (9HPT) | Measure of upper extremity function | 0 weeks, 12 weeks, 24 weeks, 64 weeks | 
| MRI T1 3D BRAVO scan | Cortical volume, volumes of white matter and deep grey matter | 0 weeks, 12 weeks, 24 weeks | 
| MRI T2 FLAIR 3D Cube scan | Lesion volume | 0 weeks, 12 weeks, 24 weeks | 
| Diffusion weighted image (DWI) | structural connectivity using graph theoretical measures; diffusion tensor image parameters | 0 weeks, 12 weeks, 24 weeks | 
| Synthetic MRI | Contrast weighted images based on measurements of tissue properties from a single acquisition | 0 weeks, 12 weeks, 24 weeks | 
| resting-state EEG | functional connectivity using graph theoretical measures | 0 weeks, 12 weeks | 
| task-related EEG - auditory oddball paradigm | functional connectivity using graph theoretical measures, event-related potentials | 0 weeks, 12 weeks | 
| task-related EEG - adjusted SDMT paradigm | functional connectivity using graph theoretical measures, event-related potentials | 0 weeks, 12 weeks | 
| task-related EEG - n-back paradigm | functional connectivity using graph theoretical measures, event-related potentials | 0 weeks, 12 weeks | 
| functional MRI - resting-state | cortical activity (BOLD) | 0 weeks, 12 weeks, 24 weeks | 
| functional MRI - auditory oddball paradigm | event-related fMRI | 0 weeks, 12 weeks, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, cognitive rehabilitation, cognitive-motor rehabilitation, telerehabilitation