Cooling, Exercise, Multiple Sclerosis, Neurological Rehabilitation, Neuronal Plasticity
Conditions
Brief summary
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
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.
Interventions
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.
Sponsors
Multiple Sclerosis Society of Canada
Memorial University of Newfoundland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcome assessor will be blinded to group allocation, and will not be involved in conducting the training intervention.
Intervention model description
This is an assessor-blinded Randomized Controlled Trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fast walking speed | 12 weeks | Gait velocity (cm/s) measured while walking at fast pace |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal oxygen consumption during graded exercise test | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | VO2max |
| Multiple Sclerosis Impact Scale-29 | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 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'. |
| Fatigue Severity Scale | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 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. |
| Hospital Anxiety and Depression Scale | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | A self-reported rating scale of severity of mood symptoms ranging from 0-21 with higher score indicating more symptoms. |
| Spatiotemporal parameters of gait measured while walking at self-selected pace | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | Walkway outputs include step length and width (cm), double support time (%), symmetry (ratio between affected and less-affected sides) |
| Symbol Digit Modality Test | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | Cognitive impairment |
| Transcranial Magnetic Stimulation | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | Corticospinal excitability |
| Serum Insulin-like growth factor-1 (IGF-1) | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | Resting and exercise-induced serum levels of IGF-1 in response to the 12-week exercise intervention |
| Structural and functional brain changes on Magnetic Resonance Imaging (MRI) | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | 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. |
| Montreal Cognitive Assessment | Following completion of the 12-week exercise intervention and 3-months post-exercise intervention | Measures overall cognitive function with score ranging from 0 to 30 with higher scores indicating higher executive function |
Countries
Canada
Outcome results
None listed