Early Exercise Efforts in Multiple Sclerosis
Early Exercise Efforts in Multiple Sclerosis
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.
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.
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