Aerobic Exercise and Brain Health in Multiple Sclerosis
Condition: Multiple Sclerosis; Brain Atrophy; Cognitive Impairment
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      The purpose of the project is to investigate how aerobic exercise affects brain volume,
      specific brain regions, neurotrophins and cognition in patients with multiple sclerosis.

      The study will be a single blinded randomized controlled trial with a 6 months intervention.

      It is hypothesized that aerobic exercise can slow down brain atrophy, increase the size of
      hippocampus, upregulate the secretion of neurotrophins and improve cognitive performance in
      people with multiple sclerosis.
    

Detailed description: 
      Multiple Sclerosis (MS) is a physically and cognitively disabling, chronic autoimmune disease
      of unknown etiology. It is the most common neurological disease affecting young adults in
      Western countries. According to the Danish MS Registry the prevalence has increased markedly
      over the last 40 years for particularly women, and today there are approximately 14.000
      patients with MS (PwMS) in Denmark.

      The pathological hallmark of MS is sclerotic plaque. Plaques in the central nervous system
      (CNS) can be detected in vivo using magnetic resonance imaging (MRI). Both the accumulation
      of lesions and the accelerated whole-brain atrophy correlate with the progressing physical
      and cognitive disabilities that clinically characterize PwMS.

      The disease causes damage of both white and grey matter in the CNS, leading to whole brain
      atrophy and topographically specific atrophy within the hippocampus and the frontal and
      temporal cortices. The degradation of the CNS manifests as cognitive and physical disability.
      Cognitive impairment is estimated to affect up to 65% of PwMS, making it one of the most
      common and disabling symptoms of MS. Medical therapies for cognitive impairment in MS have so
      far proved ineffective. Collectively, the prevalence, impact and missing treatments highlight
      the importance of alternative approaches towards preservation of cognitive function. Despite
      equivocal findings, aerobic exercise represents a promising approach towards preservation or
      even expansion of hippocampal volume and cognitive functioning in MS. No longitudinal
      randomized controlled trial (RCT) study has so far applied the MRI technique when evaluating
      the potential neuro-protective effect of exercise on brain structure and function in MS.
      Also, given the scarcity of effective treatments for cognitive impairment in MS, a
      longitudinal exercise intervention evaluating the potential effect of aerobic exercise on
      cognition is urgently needed in MS.

      The purpose of the present project is to investigate how aerobic exercise affects brain
      volume, specific brain regions, neurotrophins and cognition in PwMS.

      It is hypothesized that aerobic exercise can slow down brain atrophy, increase the size of
      hippocampus, upregulate the secretion of neurotrophins and improve cognitive performance in
      people with MS.

      The study will be a single blinded RCT. The exercise intervention will contain 6 months of
      aerobic training (bicycling, rowing and cross trainer) performed two times a week at moderate
      to high intensity and under supervision. The control group will be "living as usual" and will
      be offered the same exercise intervention after a 6 month period. A total of approximately 85
      PwMS will be expected to be enrolled. The primary outcome of the study will be brain atrophy
      determined by MRI.

      The current interdisciplinary project aims to document and understand the possible
      neuro-protective effects of exercise in MS. This would be of high relevance to PwMS (and
      other neurological pathologies). From a societal perspective it would help optimize MS
      rehabilitation and subsequently reduce MS related costs due to disability. In case of
      positive findings, this would provide the first convincing human evidence of a disease
      modifying effect of exercise in MS.
    

Intervention name(s): Aerobic exercise
Intervention type(s): Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment