Early Exercise Efforts in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Exercise as a Supplemental Treatment Strategy Early in the Disease Course of Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03322761
• Other study ID #: Morten_Riemenschneider_PhD
• Status: Completed
• Phase: N/A
• Start date: April 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2021
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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.

Locations

Country	Name	City	State
Denmark	Section for Sport Science, Department of Public Health, University of Aarhus	Aarhus

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Region of Southern Denmark, University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (7)

Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7. — View Citation

Dalgas U, Stenager E, Ingemann-Hansen T. Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Mult Scler. 2008 Jan;14(1):35-53. Epub 2007 Sep 19. Review. — View Citation

Elovaara I. Early treatment in multiple sclerosis. J Neurol Sci. 2011 Dec;311 Suppl 1:S24-8. — View Citation

Kjølhede T, Siemonsen S, Wenzel D, Stellmann JP, Ringgaard S, Pedersen BG, Stenager E, Petersen T, Vissing K, Heesen C, Dalgas U. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2018 Sep;24(10):1356-1365. doi: 10.1177/1352458517722645. Epub 2017 Jul 28. — View Citation

Patwardhan MB, Matchar DB, Samsa GP, McCrory DC, Williams RG, Li TT. Cost of multiple sclerosis by level of disability: a review of literature. Mult Scler. 2005 Apr;11(2):232-9. Review. — View Citation

Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014 Feb;89(2):225-40. doi: 10.1016/j.mayocp.2013.11.002. Review. — View Citation

Ziemssen T, De Stefano N, Sormani MP, Van Wijmeersch B, Wiendl H, Kieseier BC. Optimizing therapy early in multiple sclerosis: An evidence-based view. Mult Scler Relat Disord. 2015 Sep;4(5):460-469. doi: 10.1016/j.msard.2015.07.007. Epub 2015 Jul 17. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Functional capacity, Six-minute walk test (6MWT)	Distance covered during a six-minute maximal walking test	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Functional capacity, Six-spot-step-test (SSST)	SSSt is a measure of walking ability, balance and coordination. Measured as the time to complete the six-spot course.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Functional capacity, Accelerometry	Measurement of level of physical activity by wearing a accelerometer for 7 days at each timepoint. Measured in counts/min.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Aerobic capacity	Maximal oxygen uptake test on bike ergometer, measured by indirect calorimetry.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Cognition, Symbol Digit Modality Test (SDMT)	Assessment of cognitive function (processing speed), with a higher number of correct answers in the test representing better cognitive function.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Cognition, Paced Auditory Serial Addition Test (PASAT)	Assessment of cognitive function (processing speed and memory), with a higher number of correct answers in the test representing better cognitive function.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Cognition, Selective Reminding Test (SRT)	Assessment of cognitive function (memory), with a higher number of correct answers in the test representing better cognitive function.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Short Form Health Survey 36 (SF-36)	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.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Multiple Sclerosis Impact Scale 29 (MSIS-29)	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.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Multiple Sclerosis Walking Scale 12 (MSWS-12)	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.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Modified Fatigue Impact Scale (MFIS)	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.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Number of lesions	Number of lesions, measured by MRI-scanning.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Lesion load	Volume of lesions, measured by MRI-scanning.	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Kurtosis	MRI-measure of microstructural changes in the brain	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Other	Inflammation	Blood samples will be analyzed for key inflammatory cytokines	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Primary	Change in Annual Relapse Rate (ARR)	Number of relapses, registered and validated by neurologist, on annual basis	ARR, 1 year intervention; 1 year follow up.
Primary	Percentage brain volume change	Brain atrophy will be measured from MRI-scans	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Secondary	Multiple Sclerosis Functional Composite (MSFC)	Composite score from Timed 25-Feet Walk Test (T25FWT), 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Test (PASAT)	Baseline, 24 weeks, after 1 year intervention, and again at 1 year follow up.
Secondary	Expanded Disability Status Scale (EDSS) score	Disability status score assessed and registered by neurologist. The scale ranges from 0-10 in 0.5 unit increments representing higher levels of disability.	Baseline, after 1 year intervention, and again at 1 year follow up.