Clinical trial NCT01611987: The Role of Exercise in Modifying Outcomes for People With Multiple Sclerosis
Official title: The Role of Exercise in Modifying Outcomes for People With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: McGill University
Sponsor class: OTHER
First posted: 2012-06-05
Enrollment: 240
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite the benefits of exercise and physical activity people with Multiple Sclerosis (MS) are relatively inactive. Physical activity is important for persons with disabilities to maintain physical function. A lack of physical activity can contribute to heart disease, osteoporosis, obesity, and diabetes. At the moment, the best way for people with MS to exercise and be physical activity is unknown. People with MS report not knowing what to do. This is a barrier to exercise.

The global aim of this study is to contribute evidence for the role of targeted exercise in altering MS outcomes over time. The design is a randomized controlled trial (RCT). The primary research question is to what extent does an MS Tailored Exercise Program (MSTEP) result in greater improvements in exercise capacity and related outcomes in comparison to a program based on general guidelines for exercise among people with MS who are sedentary and wish to engage in exercise as part of MS self-management. The primary outcome for this question is exercise capacity measured using cycle ergometry. However exercise efficiency, functional ambulation, strength, components of quality of life including frequency and intensity of fatigue symptoms, mood, global physical function, health perception, and illness intrusiveness, will also be measured as components of a global response outcome. The first confirmatory hypothesis is that MSTEP will result in a greater proportion of people making clinically relevant gains (at least 10% change) in exercise capacity than with general guidelines after 12 months of intervention; a secondary hypothesis is that, while there may be some decline in exercise capacity among individuals from end of intervention to follow-up one year later, the decline will be greater in the general guideline group augmenting the difference between groups in the proportion making 10% change from study entry to 24 months. In other words, gains will be maintained more for the MSTEP group over the general guideline group.

An exploratory hypothesis is that more of the targeted outcomes will improve with the MSTEP program than the general guideline approach. An explanatory hypothesis is that these gains will be accompanied by reports of greater exercise enjoyment and exercise self-efficacy (confidence) with the MSTEP program than with the general guideline program leading to more consistent exercise engagement and improved long-term adherence.

Detailed description: The proposal is for an assessor-blind, parallel-group, stratified, randomized controlled trial. Potential participants will be identified from the population of persons enrolled in 3 MS clinics in the Montreal area and in 3 clinics in Toronto. All persons who are known to be ambulatory and not to have co-morbidity preventing exercise engagement or capacity to consent will be informed of the study in writing and will be invited for an assessment to determine eligibility for entry into the trial. Those consenting will be randomly assigned to either the MSTEP program or the general exercise guideline program. The intervention period will be one year with follow-up to a second year.

The investigators are targeting a sample size of 120 per group (total 240), which would be sufficient to detect RR of \> 1.5 with 80% power. Sample size estimated using pc-size software. The sample size takes into account that drop-outs will inflate the variance of outcomes as multiple imputation will be used to deal with missing data.

The main analysis will be logistic regression to test the main hypothesis related to the superiority of the MSTEP program based on a greater proportion of people making a clinically relevant gain in exercise capacity at 1 year. A secondary outcome will be the differences in proportions at 2 years also using logistic regression. The analysis will be based on intention-to-treat and all persons will be analysed in the groups to which they were randomized.

A secondary analysis will estimate the impact of exercise on the other relevant outcomes. For this approach, each outcome will be converted to a binary response variable based on published clinically meaningful changes and generalized estimating equations (GEE) will be used to test the rate of response in the MSTEP program to the rate of response in the general guideline approach. Multiple outcomes improves the efficiency of the study as the total number of data points is equivalent to the total n multiplied by the number of tests and reduced by the extent to which the outcomes are correlated. Highly correlated outcomes will make the effective sample size smaller than less strongly correlated outcomes. If there is a statistically significant effect of the intervention, then and only then, can the effects of the separate outcomes be interpreted as real.

The results of the trial will be used to develop guidelines for exercise for MS. The investigators are in the process of copyrighting the name of the program (MSTEP). Upon publication of the findings, the description of content will be made available at no cost. If proven effective, a training guide for professionals and patients will be produced most likely taking advantage of the end-of-grant Knowledge Translation (KT) Supplement. Note: The investigators have been funded by the KT supplement to produce a general guide for people with MS, entitled: Getting on with Your Life with MS. The knowledge generated can be used by people with MS and health professional to promote exercise engagement.

Eligibility criteria: Inclusion Criteria:

* be community dwelling individuals aged 19 -65 who have been diagnosed after 1994 with MS or CIS;
* be able to speak and read English or French;
* be capable of walking 100 meters without a walking aid (EDSS ≤ 5.5), even if they do use an aid for daily activities.

Exclusion Criteria:

* have an additional illness that restricts their function; and/or
* had suffered at least one relapse during the past 30 days (as defined by Polman) as this may affect physical activity/exercise participation.

Primary outcomes:
measure: oxygen consumption
timeFrame: 3 timepoints: baseline, at 12 monts, at 24 months
Secondary outcomes:
measure: muscle strength measured with Biodex
timeFrame: 3 timepoints: Baseline, at 12 months, at 24 months
measure: 6 Minute Walk test (6MWT)
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Anaerobic leg power
timeFrame: 1 timepoint: baseline
measure: Patient Determined Disease Steps (PDDS)
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Change in fatigue levels
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Rand 36
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: EQ-5D
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Patient generated Index
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Exercise Self-Efficacy Scale
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Change in perception about exercise benefits and exercise barrier
timeFrame: 5 timepoints: at baseline, at 6 months, at 12 months, at 18 months, at 24 months
measure: Modified Canadian Aerobic Fitness test
timeFrame: 3 timepoints: 3 month, 6 month and 18 month
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Rehabiliation Institute
state: Ontario
city: Montreal
country: Canada
facility: CHUM
state: Quebec
city: Montreal
country: Canada
facility: Muhc - Mnh
state: Quebec
Study officials:
affiliation: McGill University
name: Nancy E Mayo, PhD
role: PRINCIPAL_INVESTIGATOR
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