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Early Exercise Efforts in Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT03322761
Recruitment Status : Recruiting
First Posted : October 26, 2017
Last Update Posted : April 17, 2018
Sponsor:
Collaborators:
University of Southern Denmark
Region of Southern Denmark
Information provided by (Responsible Party):
University of Aarhus

Tracking Information
First Submitted Date  ICMJE October 16, 2017
First Posted Date  ICMJE October 26, 2017
Last Update Posted Date April 17, 2018
Actual Study Start Date  ICMJE April 1, 2018
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
  • Change in Annual Relapse Rate (ARR) [ Time Frame: ARR, 1 year intervention; 1 year follow up. ]
    Number of relapses, registered and validated by neurologist, on annual basis
  • Percentage brain volume change [ Time Frame: Baseline, after 1 year intervention, and again at 1 year follow up. ]
    Brain atrophy will be measured from MRI-scans
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03322761 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
  • Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Composite score from Timed 25-Feet Walk Test (T25FWT), 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Test (PASAT)
  • Expanded Disability Status Scale (EDSS) score [ Time Frame: Baseline, after 1 year intervention, and again at 1 year follow up. ]
    Disability status score assessed and registered by neurologist. The scale ranges from 0-10 in 0.5 unit increments representing higher levels of disability.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 23, 2017)
  • Functional capacity, Six-minute walk test (6MWT) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Distance covered during a six-minute maximal walking test
  • Functional capacity, Six-spot-step-test (SSST) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    SSSt is a measure of walking ability, balance and coordination. Measured as the time to complete the six-spot course.
  • Functional capacity, Accelerometry [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Measurement of level of physical activity by wearing a accelerometer for 7 days at each timepoint. Measured in counts/min.
  • Cognition, Symbol Digit Modality Test (SDMT) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Assessment of cognitive function, with a higher number of correct answers in the test representing better cognitive function.
  • Short Form Health Survey 36 (SF-36) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Questionnaire assessing health status. The SF-36 consists of eight subscales, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.
  • Multiple Sclerosis Impact Scale 29 (MSIS-29) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Questionnaire assessing the impact of the disease. 20 questions measure the physical impact, and 9 questions measure the psychological impact. Each question is scored from 1-5. A greater score is equal to a larger impact.
  • Multiple Sclerosis Walking Scale 12 (MSWS-12) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Questionnaire assessing the impact of the disease on walking. Each question is scored from 1-5 and then summed and transformed to a 0-100 scale. Higher scores indicate a greater impact on walking.
  • Modified Fatigue Impact Scale (MFIS) [ Time Frame: Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up. ]
    Questionnaire assessing the effects of fatigue on physical, cognitive and psychosocial functioning. The score of the MFIS is the sum of the scores for the 21 items. A higher score represents a higher impact of fatigue, in general or in relation to one of the above mentioned areas.
  • Inflammation [ Time Frame: Baseline, after 1 year intervention, and again at 1 year follow up. ]
    Blood samples will be analyzed for key inflammatory cytokines
  • Number of lesions [ Time Frame: Baseline, after 1 year intervention, and again at 1 year follow up. ]
    Number of lesions, measured by MRI-scanning.
  • Lesion load [ Time Frame: Baseline, after 1 year intervention, and again at 1 year follow up. ]
    Volume of lesions, measured by MRI-scanning.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Early Exercise Efforts in Multiple Sclerosis
Official Title  ICMJE Exercise as a Supplemental Treatment Strategy Early in the Disease Course of Multiple Sclerosis
Brief Summary

This study seeks to investigate whether early exercise efforts can expand the use of exercise in Multiple sclerosis (MS), from symptom treatment only, to early supplementary disease-modifying treatment.

The study will be conducted in a randomized and controlled manner, with single blinding. Participants will be allocated to either a systematic aerobic exercise intervention or an educational programme on exercise and physical activity. Both interventions will last 1 year, and involve a 1 year follow-up period.

It is hypothesized that early exercise efforts can modify the disease activity and disability progression.

Detailed Description

Multiple Sclerosis (MS) is an autoimmune and neurodegenerative disease in the central nervous system (CNS), characterized by a complex pathogenesis and heterogeneous symptoms. The histopathological hallmark of the disease is sclerotic lesions. These inflammatory lesions manifests as disabling relapses, and the number of relapses in the first few years after disease onset is associated with progression of disability, with a higher number of relapses leading to a more rapid progression. In addition, diffuse neurodegeneration seems to occur early in the disease, and even though it is not always clinically evident it is associated with disease progression. A reduction in relapse rate and neurodegeneration early in the MS disease course may slow the progression of disabilities and can possibly reduce overall disease burden. For the individual person with MS (pwMS) a reduction in overall disease burden will often improve quality of life, and since MS is a lifelong disease this is of great interest. Preventing disability in pwMS is also highly relevant in a societal perspective, as it lowers the large costs associated with increased disability. As a consequence, the importance of early treatment have been emphasized.

Treatment of MS have seen great advances in the recent years, resulting in an increasing number of available disease-modifying treatments (DMT). Despite the fact that the current DMTs favourable alter a number of clinical outcomes and the course of the disease, it is still a serious and deteriorating condition with significant disease activity, impaired neurological functions and thus progression of disabilities. New and supplemental treatment strategies are therefore still warranted, and exercise have gained attention as a safe and tolerable rehabilitation strategy. Recently, exercise furthermore have gained substantial attention, as the first indications of neuroprotective and disease-modifying effects of exercise has been published. However, despite the focus on early treatment in medical DMTs no studies have investigated the effects of exercise as a supplemental treatment strategy early in the disease course of MS.

Consequently, the purpose of this study is to investigate the effects of early exercise efforts on disease activity and disability progression. In a sub-group the effects will furthermore be investigated on brain volume, specific brain regions, and inflammation.

It is hypothesized that early exercise efforts can modify the disease activity and disability progression, by reducing the relapse rate, the progression of Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) scores. The rate of brain atrophy and the lesion load, obtained by MRI scans, is also hypothesized to be reduced. This is expected to be due to an exercise-induced reduction in inflammation.

The study will be a randomised and controlled study with randomisation to either an systematic aerobic exercise intervention or an educational programme on exercise and physical activity. Both interventions are in addition to standard treatment, and will last 1 year. The exercise intervention will consist of 2 supervised exercise sessions per week in the complete duration of the study, while the standard treatment plus exercise education program will consist of 4 educational sessions on the health benefits associated with exercise and physical activity held every third month throughout the intervention period. The training in the exercise group will be aerobic exercise (running, cycling, rowing or on a cross-trainer) planned by exercise physiologists and performed in a progressive manner. To allow handling of a large number of participants, who is also geographically spread, the exercise intervention will be locally anchored, but at the same time supervised by student employees from Section for Sports Science and controlled by internet- and telephonic communication. In addition to the two intervention groups, data from The Danish MS registry will serve as population based standard treatment control data. All groups will be followed up 1 year after cessation of the interventions.

To set the estimated number of participants a two-sample two-sided power calculation has been conducted. The basis for this calculation is an report from Tallner et al. who have shown a difference in relapse rate during a two-year period (equal to our 1 year intervention, and 1 year follow-up) of 0.65 relapses between physically active and physically inactive MS patients (active: 0.95 +/- 0.97 relapses in 2 years ; inactive: 1.60 +/- 1.64 relapses in 2 years). 83 patients with MS should be enrolled in each intervention group (a 20% drop-out rate has been included). Newly published data on the brain atrophy in percentage of total brain volume after 24 weeks of resistance training have been the basis for a similar calculation of the number of participants in the sub-group, from whom MRI-scans and blood samples will be obtained. 41 participants from each intervention group should form this sub-group.

MS is a complex disease with heterogenous symptoms, and by combining the disciplines of exercise physiology, neurology and radiology this study can be the first long-term and large-scale exercise study to investigate the possible neuroprotective and disease-modifying effects of exercise when initiated early in the disease course of MS. Consequently, this project has the potential to change present clinical practice and generate further attention to exercise, not only as symptom treatment, but also as an supplemental disease-modifying treatment strategy early in the course of MS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Combination Product: Systematic exercise training
    Combination of standard medical treatment and systematic early exercise training in persons with MS.
  • Behavioral: Educational program
    Informations regarding health benefits of physical activity and exercise.
Study Arms  ICMJE
  • Experimental: Systematic exercise training
    Two weekly supervised aerobic exercise trainings for 48 weeks. The training will be planned by exercise physiologists, and performed in a progressive manner.
    Intervention: Combination Product: Systematic exercise training
  • Active Comparator: Educational program
    Educational program on physical activity and health, consisting of four educational sessions in the intervention period.
    Intervention: Behavioral: Educational program
  • No Intervention: Standard treatment alone
    Data from The Danish MS Registry will serve as control-data for standard treatment alone.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2017)
166
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed consent
  • Definite diagnosis with Relapsing remitting multiple sclerosis (RRMS)
  • No more than 2 years since diagnosis
  • Expectedly able to carry out high intensity aerobic training
  • Able to transport themselves to and from training sessions

Exclusion Criteria:

  • Pregnancy
  • Dementia, alcohol abuse, or pacemaker
  • Metallic implants, hindering MRI-scans
  • Comorbidities hindering participation in high intensity aerobic training
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Morten Riemenschneider, MSc +4522855185 mori@ph.au.dk
Contact: Ulrik Dalgas, PhD +4540123039 dalgas@ph.au.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03322761
Other Study ID Numbers  ICMJE Morten_Riemenschneider_PhD
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University of Aarhus
Study Sponsor  ICMJE University of Aarhus
Collaborators  ICMJE
  • University of Southern Denmark
  • Region of Southern Denmark
Investigators  ICMJE
Principal Investigator: Morten Riemenschneider, MSc Section for Sport Science, Department of Public Health, Aarhus University
PRS Account University of Aarhus
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP