Influence of different rehabilitative aerobic exercise programs on (anti-) inflammatory immune signalling, cognitive and functional capacity in persons with MS - study protocol of a randomized controlled trial

BMC Neurol. 2019 Mar 8;19(1):37. doi: 10.1186/s12883-019-1267-9.


Background: Studies have shown positive effects of therapeutic exercise on motor- and cognitive function as well as on psychosocial outcomes in persons with multiple sclerosis (MS). 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. The primary objective of this trial is to investigate the acute and chronic effects of different exercise modalities on (anti-)inflammatory immune signalling as well as on cognitive and functional capacity in persons with MS.

Methods: A two armed single-blind randomized controlled design will investigate 72 persons with relapsing remitting or secondary progressive MS (EDSS 3.0-6.0), during 3 weeks of inpatient rehabilitation. Participants will be randomized into either a high-intensity interval training (HIIT) or a moderate continuous training group; the latter represents the local standard therapy (ST). Both groups will exercise 3x per week. The HIIT group will perform 5 × 1.5-min high-intensive exercise bouts at 95-100% of their maximum heart rate (HRmax) followed by active breaks of unloaded pedalling (60% HRmax) for 2 min. In contrast, the ST group will exercise for 24 min continuously at 65% of HRmax. The proportion of circulating regulatory T-cells will be measured as primary outcome. Secondary outcomes comprise numbers and proportions of further immune cells including Th17-cells, soluble factors ((anti-) inflammatory cytokines, tryptophan metabolites), endurance capacity, cognitive performance, processing skills for activities of daily living, fatigue, depression and healthcare-related quality of life. Outcomes will be assessed before (T0) and after (T3) the 3-week exercise intervention program. Blood samples of T0 will be taken immediately before the first exercise session. Additionally, blood samples for the soluble factors will be collected immediately after (T1) and three hours (T2) after the first exercise session of each group.

Discussion: This study will be the first to investigate both acute and chronic effects of aerobic exercise on immune function and disease associated biomarkers in persons with MS. Combining biological analyses with cognitive and functional capacity assessments may contribute to a better understanding of responses to rehabilitative training, needed to improve exercise recommendations for persons with MS.

Trial registration: This trial was prospectively registered at ( NCT03652519 ; 29 August 2018).

Keywords: Cognition; Exercise; High-intensity interval exercise; Immune signalling; Inflammation; Kynurenine pathway; Multiple sclerosis; Rehabilitation.

Publication types

  • Clinical Trial Protocol
  • Randomized Controlled Trial

MeSH terms

  • Activities of Daily Living
  • Adult
  • Biomarkers / blood
  • Cognition*
  • Cytokines / blood
  • Exercise Therapy / methods*
  • Exercise Tolerance
  • Fatigue / etiology
  • Fatigue / prevention & control
  • High-Intensity Interval Training*
  • Humans
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Chronic Progressive / psychology
  • Multiple Sclerosis, Chronic Progressive / rehabilitation*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / psychology
  • Multiple Sclerosis, Relapsing-Remitting / rehabilitation*
  • Quality of Life
  • Single-Blind Method
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / metabolism
  • Time Factors
  • Treatment Outcome
  • Tryptophan / blood


  • Biomarkers
  • Cytokines
  • Tryptophan

Associated data