Comparison of Vigorous Versus Low Intensity Cool Room Treadmill Training in People With Multiple Sclerosis

Study Overview
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Brief Summary
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New research in animal models of MS suggests that greater training intensity is required to restore lost functions. We have developed and tested vigorous intensity cool room treadmill training that people with MS who have fatigue and heat-sensitivity can tolerate. This study will focus on the appropriate dosage of training.

Detailed Description
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Our previous research showed that vigorous aerobic training in a room cooled to 16°C can improve walking and measures of brain plasticity among people with MS related walking disability, especially in those who had fatigue and heat sensitivity. As a next step, we will compare our novel vigorous intensity cool room treadmill training to low intensity cool room treadmill walking and determine whether intensity is important in order to improve brain repair and restore walking among people with MS. Our first objective is to compare the effects of 12 weeks of vigorous versus low intensity training on walking. Our second objective is to determine whether treadmill training alters indicators of brain repair. We hypothesize that the cool room vigorous training will result in greater increases in walking and less fatigue, which will be sustained at follow-up. We also hypothesize that improvements will align with less brain inhibition (shortened CSP measured using Transcranial Magnetic Stimulation) and greater upregulation of the neurotrophin IGF-1.

Official Title
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Training to Restore Walking and Promote Nervous System Repair in Multiple Sclerosis: RCT to Determine the Importance of Intensity

Conditions
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Multiple Sclerosis, Neurological Rehabilitation, Exercise, Neuronal Plasticity, Cooling

Intervention / Treatment
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* Other: Body-weight supported treadmill training in a room cooled to 16°C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: people with a confirmed diagnosis of relapsing-remitting or progressive MS older than 18 and less than 70 years of age able to walk at least 10 meters with use of walking aids (Expanded Disability Status Scale (EDSS) <7.0) must be stable without relapse for at least 90 days Exclusion Criteria: currently attending physical rehabilitation functional community ambulators (gait speed>120 cm/s) a relapse of MS

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: This is an assessor-blinded Randomized Controlled Trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low Intensity Group<br>Less than 40% Heart Rate Reserve | Other: Body-weight supported treadmill training in a room cooled to 16°C<br>* Exercise will be performed on a treadmill using an overhead harness for safety in a temperature controlled-room at 16°C with 1:1 supervision. The high intensity group will maintain vigorous intensity with a target workload >60% of heart rate reserve for 30 min (plus 5min warm up and 5min cool down) while the low-intensity group will walk at mild intensity (<40% heart rate reserve) for the same duration. Heart rate, blood pressure, and rating of perceived exertion will be recorded throughout to monitor for potential adverse events and to ensure that target training zone heart rates are maintained. The intervention is 3 times per week for 12 weeks, with a 3-month run-in observational period to confirm disease stability, and 3-month follow-up to determine the sustainability of effects.<br>|
| Experimental: Vigorous Intensity Group<br>More than 60% Heart Rate Reserve | Other: Body-weight supported treadmill training in a room cooled to 16°C<br>* Exercise will be performed on a treadmill using an overhead harness for safety in a temperature controlled-room at 16°C with 1:1 supervision. The high intensity group will maintain vigorous intensity with a target workload >60% of heart rate reserve for 30 min (plus 5min warm up and 5min cool down) while the low-intensity group will walk at mild intensity (<40% heart rate reserve) for the same duration. Heart rate, blood pressure, and rating of perceived exertion will be recorded throughout to monitor for potential adverse events and to ensure that target training zone heart rates are maintained. The intervention is 3 times per week for 12 weeks, with a 3-month run-in observational period to confirm disease stability, and 3-month follow-up to determine the sustainability of effects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fast walking speed | Gait velocity (cm/s) measured while walking at fast pace | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spatiotemporal parameters of gait measured while walking at self-selected pace | Walkway outputs include step length and width (cm), double support time (%), symmetry (ratio between affected and less-affected sides) | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Maximal oxygen consumption during graded exercise test | VO2max | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Multiple Sclerosis Impact Scale-29 | The Multiple Sclerosis Impact Scale-29 provides physical and psychological sub-scales. Using a Likert scale, participants indicate the degree to which problems, such as 'moving about' and 'balance' affect them from 'not at all' to 'extremely'. | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Fatigue Severity Scale | A 9-item questionnaire, which assesses the severity of fatigue with items scored on a 7-point scale, '1 = strongly disagree' and '7 = strongly agree'. The minimum and maximum score possible are 9 and 63 respectively. Another reporting method is the mean of all scores from all 9-items, with minimum and maximum score possible being 1 and 7 respectively. | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Hospital Anxiety and Depression Scale | A self-reported rating scale of severity of mood symptoms ranging from 0-21 with higher score indicating more symptoms. | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Montreal Cognitive Assessment | Measures overall cognitive function with score ranging from 0 to 30 with higher scores indicating higher executive function | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Symbol Digit Modality Test | Cognitive impairment | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Transcranial Magnetic Stimulation | Corticospinal excitability | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Serum Insulin-like growth factor-1 (IGF-1) | Resting and exercise-induced serum levels of IGF-1 in response to the 12-week exercise intervention | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 
| Structural and functional brain changes on Magnetic Resonance Imaging (MRI) | Standardized protocol recommended by the Canadian Dementia Imaging Group (https://www.cdip-pcid.ca/) which includes T1 and T2-weighted structural images, diffusion tensor imaging, and resting state connectivity. | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention |