Supported Treadmill Training for Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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This study is a pilot trial to evaluate the effects of supported treadmill walking in patients with primary progressive multiple sclerosis (MS) on functional and psychosocial outcomes. Patients will exercise three times per week over the course of 6 months and will be evaluated at baseline, 12 weeks and 24 weeks into the program. Follow-up testing will also be conducted 12 weeks after participants have stopped exercising to determined the lasting effects of the intervention. The investigators hypothesize that supported treadmill walking will be effective at improving physical physical function and psychosocial outcomes in patients with primary progressive MS.

Detailed Description
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The use of exercise as an adjunct to other disease modifying treatments in MS has found increasing support over the past decade. There is ample evidence that exercise therapy can improve physical measures of disability in MS, in addition to being safe and well-tolerated. However, there is a paucity of data on whether exercise is equally effective for those with primary progressive MS as it is in relapsing remitting MS. In addition, studies of exercise therapy have traditionally excluded MS patients with severe disability. There are also currently no treatments for primary progressive MS, so finding a safe disease-modifying therapy is of the utmost importance. The investigators are therefore conducting a pilot trial to evaluate the effects of exercise in the form of supported treadmill walking for patients with primary progressive MS with severe functional impairments. Six patients with primary progressive MS with high disability level will be recruited to participate in this study. Participants will exercise using body-weight supported treadmill training (BWSTT; Woodway Loco-system) which allows a portion of an individual's body-weight to be counterbalanced by an overhead pulley system. This system allows patients with limited mobility to walk upright on the treadmill with therapist assistance. Therapists trained in using the BWSTT system will guide the patients' legs through a proper gait motion and assist with lower limb control. Participants will complete 72 training sessions (30min/session, 3x/week) over the course of 24 weeks. Participants will be evaluated at baseline, 12 weeks (half-way through the training program) and 24 weeks (end of intervention). A follow-up assessment will also be performed 12 after participants have completed the training program (36 weeks). Outcome measures are described below.

Official Title
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Body-weight Supported Treadmill Training in Primary Progressive Multiple Sclerosis: A Pilot Trial

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Body-weight supported treadmill training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed, written informed consent Males or non-pregnant females, 18-60 years of age (inclusive) Clinically definite PPMS as per the diagnostic criteria of Thompson et al (2000) Expanded disability status score 5.0-8.0 (constant assistance required) Body weight <90kg (due to support limitations of treadmill) Approval from physician to participate in the exercise program Ability to tolerate upright locomotion of the body weight supported treadmill Ability to visit the different sites required for the study Ability to commit to 3 weekly training sessions for the duration of 24 weeks Exclusion Criteria: Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS Any other serious medical condition that might impair the subject's ability to walk on a treadmill and/or participate in aerobic exercise (including but not limited to: documented heart disease or unstable angina, uncontrolled cardiac dysrhythmia, chronic obstructive lung disease, recent non-traumatic fracture, osteoporosis and severe skin ulcerations) Female patients who do not agree to use effective contraceptive method(s) during the study Current use or use within the last 2 months of any on- or off-label disease-modifying therapy including IFN-β, glatiramer acetate, IV steroids, mitoxantrone, azathioprine, and cyclophosphamide Previous experience with supported treadmill training Kidney disease, peripheral vascular disease or poor circulation Inability to undergo MRI or MRI with gadolinium administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Body-weight supported treadmill training<br> | Other: Body-weight supported treadmill training<br>* Patients will undergo training using the Woodway Loco-system which consists of a treadmill with an overhead pulley system connected to a support harness. BWSTT allows patients with limited mobility to safely walk upright on a treadmill with a portion of their body weight counter balanced. Three trainers will be required to assist with the BWSTT program. Two trainers will be positioned at the lower limbs to manually guide the participant through a proper gait motion and provided lower limb control. A third trainer will stand behind the participant to provide trunk support and assist with weight shifting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Multiple Sclerosis Functional Composite (MSFC) at 12, 24 and 36 weeks | The MSFC assesses functional ability with three scales: the 25ft walk (leg strength and ambulation), the 9-hole peg test (arm strength and coordination) and the Paced Auditory Serial Addition Test (PASAT; cognition). Scores on all three measures are combined to produce a composite Z-score. | Repeat assessments: baseline, 12 weeks, 24 weeks and 36 weeks (12 weeks post-exercise follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Expanded Disability Status Scale (EDSS) at 12, 24 and 36 weeks | The EDSS provides a measure of physical and neurological function specifically in MS patients and is scored from 0-10. This will be assessed by a train neurologist. | Repeat assessments: baseline, 12 weeks, 24 weeks and 36 weeks (12 weeks post-exercise follow-up) | 
| Change from baseline in Modified Fatigue Impact Scale (MFIS) at 12, 24 and 36 weeks | The MFIS is a 21-item self-report questionnaire that evaluates fatigue overall fatigue, as well as within three categories: physical (pMFIS); cognitive (cMFIS); and psychosocial (psMFIS), over the previous 4 weeks. Scores range from 0-4 on each item with a maximum total score of 84, where higher scores indicate greater fatigue levels. | Repeat assessments: baseline, 12 weeks, 24 weeks and 36 weeks (12 weeks post-exercise follow-up) | 
| Change from baseline in Multiple Sclerosis Quality of Life-54 questionnaire at 12, 24 and 36 weeks | The MSQOL-54 is an MS-specific measure of quality of life that consists of 54 items divided into 12 multi-item scales, 2 single-item scales, and 2 composite scores (physical and mental health). | Repeat assessments: baseline, 12 weeks, 24 weeks and 36 weeks (12 weeks post-exercise follow-up) | 
| Change from baseline in brain-derived neurotrophic factor (BDNF) at 12, 24 and 36 weeks |  | Repeat assessments: baseline, 12 weeks, 24 weeks and 36 weeks (12 weeks post-exercise follow-up) | 
| Change from baseline in magnetic resonance imaging (MRI) outcomes at 24 weeks | Both standard and unconventional MRI techniques will be used to evaluate the effects of exercise on brain health. | Repeat assessments: baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treadmill exercise, rehabilitation, progressive multiple sclerosis, functional ability, quality of life, fatigue