Clinical trial NCT03652519: High-intensity Training and Its Effects on Neuroplasticity
Official title: Influence of Different Rehabilitative Aerobic Exercise Programs on (Anti-) Inflammatory Immune Signalling, Cognitive Performance and Processing Skills in Persons With MS - A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Exercise
Immune Signalling
Cognition
Health-related Quality of Life
Lead sponsor: Klinik Valens
Sponsor class: OTHER
Collaborators: name: German Sport University, Cologne
First posted: 2018-08-29
Enrollment: 72
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Definite diagnosis of MS (according to the revised McDonald criteria 2010)
* Expanded Disability Status Scale 3.0 - 6.0
* Age \> 21
* Relapsing remitting or secondary progressive MS
* Informed Consent as documented by signature

Exclusion Criteria:

* Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
* Define drugs not allowed during the study or for specific periods of time prior to the administration of the test dose,
* Women who are pregnant or breast feeding,
* Intention to become pregnant during the course of the study,
* Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
* Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
* Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
* Known or suspected non-compliance, drug or alcohol abuse,
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Participation in another study with investigational drug within the 30 days preceding and during the present study,
* Previous enrolment into the current study,
* Enrolment of the investigator, his/her family members, employees and other dependent persons

Primary outcomes:
measure: Tregs
timeFrame: Three weeks (day 0 to day 21)
Secondary outcomes:
measure: Immune status
timeFrame: Three weeks (day 0 to day 21)
measure: Soluble factors (cytokines, tryptophan metabolites, blood brain barrier markers)
timeFrame: 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)
measure: Migratory Potential of peripheral mononuclear cells (PBMC)
timeFrame: Three weeks (day 0 to day 21)
measure: Endurance capacity
timeFrame: Three weeks (day 0 to day 21)
measure: Assessment of Motor and Processing Skills (AMPS)
timeFrame: Three weeks (day 0 to day 21)
measure: Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
timeFrame: Three weeks (day 0 to day 21)
measure: Fatigue Scale of Motor and cognitive function (FSMC)
timeFrame: Three weeks (day 0 to day 21)
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Three weeks (day 0 to day 21
measure: Patient-Reported Outcome Measurement Information System (PROMIS)
timeFrame: Three weeks (day 0 to day 21)
measure: Test battery of attention (TAP)
timeFrame: Three weeks (day 0 to day 21)
Other outcomes:
Locations:
city: Valens
country: Switzerland
facility: Kliniken-Valens
state: Sankt Gallen
Study officials:
affiliation: Klinik Valens
name: Jens Bansi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joisten N, Rademacher A, Warnke C, Proschinger S, Schenk A, Walzik D, Knoop A, Thevis M, Steffen F, Bittner S, Gonzenbach R, Kool J, Bloch W, Bansi J, Zimmer P. Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021 Mar 29;8(3):e982. doi: 10.1212/NXI.0000000000000982. Print 2021 May.
citation: Joisten N, Rademacher A, Bloch W, Schenk A, Oberste M, Dalgas U, Langdon D, Caminada D, Purde MT, Gonzenbach R, Kool J, Zimmer P, Bansi J. 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.