Early Exercise Efforts in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

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.
    

Intervention name(s): Systematic exercise training; Educational program
Intervention type(s): Combination Product; Behavioral
Intervention description(s): Combination of standard medical treatment and systematic early exercise training in persons with MS.; Informations regarding health benefits of physical activity and exercise.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Multiple sclerosis; Exercise; Disease-modifying treatment; Early treatment