Clinical trial NCT02661555: Aerobic Exercise and Brain Health in Multiple Sclerosis
Official title: Effects of Aerobic Exercise on Brain Health in People With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Brain Atrophy
Cognitive Impairment
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Jascha Fonden
name: Knud and Edith Eriksens memorial fund
name: University of Southern Denmark
name: Augustinus fund
name: Masku Neurological Center
First posted: 2016-01-22
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Signed consent
* Definite MS diagnosis
* Be clarified with the diagnosis and treatment
* Expectedly able to carry out the aerobic training / test
* Expanded Disability Status Scale (EDSS) score ≤6.0
* Must be able to transport themselves to and from training sessions

Exclusion Criteria:

* Dementia, alcohol abuse or pacemaker
* Medical comorbidity such as cardiovascular, respiratory, orthopedic or metabolic disorders or other concurrent diseases causing disability and hindering participation in the intervention
* Disease relapse in a 8 week period prior to study start
* Pregnancy
* Metallic implants hindering the MRI scans.
* Expected training attendance below 85%

Primary outcomes:
measure: Percentage brain volume change
timeFrame: 0, 24 and 48 weeks
Secondary outcomes:
measure: Cognition measured by the Brief Repeatable Battery of Neuropsychological Tests
timeFrame: 0, 24 and 48 weeks
measure: Blood samples: Cytokines and neurotrophins
timeFrame: 0, 24 and 48 weeks
measure: VO2max
timeFrame: 0, 24 and 48 weeks
measure: Regional volume change changes (e.g. hippocampus, thalamus)
timeFrame: 0, 24 and 48 weeks
measure: Modified Fatigue Impact Scale
timeFrame: 0, 24 and 48 weeks
measure: Fatigue Severity Scale
timeFrame: 0, 24 and 48 weeks
measure: Major Depression Inventory
timeFrame: 0, 24 and 48 weeks
measure: Short Form 36
timeFrame: 0, 24 and 48 weeks
measure: Multiple Sclerosis Impact Scale 29
timeFrame: 0, 24 and 48 weeks
measure: 6-min walk test
timeFrame: 0, 24 and 48 weeks
measure: Six Spot Step Test
timeFrame: 0, 24 and 48 weeks
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Sport Science, Department of Public Health, Aarhus University
state: Aarhus C
Study officials:
affiliation: University of Aarhus
name: Martin L Christensen, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langeskov-Christensen M, Grondahl Hvid L, Nygaard MKE, Ringgaard S, Jensen HB, Nielsen HH, Petersen T, Stenager E, Eskildsen SF, Dalgas U. Efficacy of High-Intensity Aerobic Exercise on Brain MRI Measures in Multiple Sclerosis. Neurology. 2021 Jan 12;96(2):e203-e213. doi: 10.1212/WNL.0000000000011241. Epub 2020 Dec 1.
citation: Langeskov-Christensen M, Hvid LG, Jensen HB, Nielsen HH, Petersen T, Stenager E, Hamalainen P, Dalgas U. Efficacy of high-intensity aerobic exercise on cognitive performance in people with multiple sclerosis: A randomized controlled trial. Mult Scler. 2021 Sep;27(10):1585-1596. doi: 10.1177/1352458520973619. Epub 2020 Nov 24.