Regular physical activity is known to reduce the risk for some neurodegenerative disorders and their symptoms. Several studies have shown positive effects of therapeutic exercise interventions on motor- and cognitive function as well as psychosocial benefits in persons with multiple sclerosis (MS). To improve exercise recommendations, it is necessary to learn more about the underlying biological mechanisms. A reduction of inflammatory stress through physical exercise has been suspected as one key mechanism, mediating the positive effects of exercise in the context of MS (being a "classical" neuro-inflammatory disease). This randomized controlled trial aims to investigate the influence of two different rehabilitative endurance exercise programs (3x/week moderate vs. vigorous endurance exercise) on (1) (anti-)inflammatory immune signalling and (2) various aspects of participation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
72
Treatment in both arms consists of specific of aerobic exercise training modalities. Exercise has become an efficient strategy within rehabilitative programs and is part of a goal-orientated multidisciplinary approach to improve disability and participation in persons with MS. Recently, short and exhaustive bouts of exercise have gained much attention as a promising option in supportive care in MS.
Kliniken-Valens
Valens, Canton of St. Gallen, Switzerland
Tregs
Proportion of regulatory T-cells with higher values indicating higher levels of Inflammation.
Time frame: Three weeks (day 0 to day 21)
Immune status
Numbers and proportions of circulating immune cells associated with MS and exercise (Th17 cell, cytotoxic T-cells, naïve T-cells, memory T-cells, NK-cells, Monocytes) with higher values indicating higher levels of inflammation.
Time frame: Three weeks (day 0 to day 21)
Soluble factors (cytokines, tryptophan metabolites, blood brain barrier markers)
Soluble factors that are known to be produced or secreted in response to (acute/chronic) exercise and are suspected to modify immune homeostasis and blood brain barrier function through their inflammatory and anti-inflammatory properties. (Tryptophan, Kynurenine, Kynurenine acid, Tumor Necrosis Factor-alpha (TNF-Alpha), Interferon-gamma (IFN-Gamma), Interleukin-6 (IL-6), Matrix-metalloproteinases-2 (MMP-2), Matrix-metalloproteinases-9 (MMP-9), Interleukin-10 (IL-10), Tumor Growth Factor-beta (TGF-beta), Interleukin-17 (IL-17) with higher values indicating higher levels of Inflammation.
Time frame: Change from baseline (day 0) to directly after and 3-hours after the first exercise session (on day 0) and over 3-weeks (day 0 to day 21)
Migratory Potential of peripheral mononuclear cells (PBMC)
The migratory Potential of PBMC will be assessed by in situ zymography with higher values indicating higher Levels of Inflammation.
Time frame: Three weeks (day 0 to day 21)
Endurance capacity
Endurance capacity will be measured by peak oxygen consumption achieved in the cardiopulmonary exercise test. Higher values indicate better cardiorespiratory fitness.
Time frame: Three weeks (day 0 to day 21)
Assessment of Motor and Processing Skills (AMPS)
Processing skills of executive functions
Time frame: Three weeks (day 0 to day 21)
Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
Cognitive Performance is assessed with the BICAMS This test battery involves three tests to assess the main cognitive domains vulnerable to MS: information processing speed, verbal and visual memory. The battery includes the Symbol Digit modalities Test (SDMT), Californian Verbal Learning Test-II (CVLT-II) and the Brief Visuospatial Memory Test revised (BVMT-R). Processing speed is the most relevant test and is assessed by the SDMT where the patients have 90s to voice numbers as rapidly as possible that were associated with target symbols within a grid printed at the top of a Stimulus page. The final score is the correct number of substitutions in 90 s, and scores ranges between 0 and 110. Higher scores indicating better cognition.
Time frame: Three weeks (day 0 to day 21)
Fatigue Scale of Motor and cognitive function (FSMC)
Changes of motor and cognitive fatigue on a 5-point Linkert-Scale. Max 50 Points for subsclaes, 100 Points for the Total score. Cut-off for fatigue is set for the total score at 43 and for the motoric and cognitive subscores at 22 with higher values participants being more fatigued.
Time frame: Three weeks (day 0 to day 21)
Hospital Anxiety and Depression Scale (HADS)
Changes of anxiety and depression over three weeks training on a 4-point Linkert-Scale scored 0-3. Max 21 Points for each subsclae, cut off for anxiety and Depression are set at 7 Points higher values represent more anxiety and Depression.
Time frame: Three weeks (day 0 to day 21
Patient-Reported Outcome Measurement Information System (PROMIS)
Changes of a 4-point Likert scale will provide information about the participants' healthcare-related quality of life with higher scores indicating better Quality of life.
Time frame: Three weeks (day 0 to day 21)
Test battery of attention (TAP)
Executive functions are assessed through the reaction time of the Go/No Go tasks of the TAP. Higher reaction times indicate better executive fuctionning.
Time frame: Three weeks (day 0 to day 21)
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