Multiple SclerosisTRAINUVIMABNCT03652519
High-intensity Training and Its Effects on Neuroplasticity
A study testing Exercise Training in people with Multiple Sclerosis, run by Klinik Valens at 1 site in Switzerland.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Exercise Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteSwitzerland
- Study dates
- 21 Nov 2018to 11 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Multiple Sclerosis
- Being tested
- Exercise Training
- Keywords
- Exercise, Immune Signalling, Cognition, Health-related Quality of Life
- Medical subject headings
- Multiple Sclerosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise TrainingBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| High-intensity Interval Training (HIIT) | Experimental | Participants of the HIIT group will exercise three times per week over a period of three weeks (inpatient rehabilitation) on a cycle ergometer. Exercise intensity will be regulated and heart rate controlled based on the achieved maximum heart rate (HRmax) assessed during the initial Cardiopulmonary Exercise Testing. Each exercise session will last 30 minutes and will be started and finalized with three minutes at low intensity (50% HRmax, warm-up / cool-down). During each exercise session, participants of the HIIT group will perform 5x one-and-a-half Minute high-intensive exercise bouts at 95-100% of their HRmax followed by active breaks of unloaded pedalling over 2 minutes with the aim to achieve 60% HRmax. Receives: Behavioral: Exercise Training |
| Moderate Continous Training (ST) | Active comparator | Participants of the ST group will exercise three times per week over a period of three weeks (inpatient rehabilitation) on a cycle ergometer. Exercise intensity will be regulated and heart rate controlled based on the achieved maximum heart rate (HRmax) assessed during the initial Cardiopulmonary Exercise Testing. Each exercise session will last 30 minutes and will be started and finalized with three minutes at low intensity (50% HRmax, warm-up / cool-down). During each exercise session, participants of the ST group will exercise 30 minutes continuously at 65% of HRmax. This moderate continous training program represents the standard care at the local rehabilitation clinic. Receives: Behavioral: Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tregs
Proportion of regulatory T-cells with higher values indicating higher levels of Inflammation.
Measured: Three weeks (day 0 to day 21)
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Three weeks (day 0 to day 21)
Assessment of Motor and Processing Skills (AMPS)
Processing skills of executive functions
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Three weeks (day 0 to day 21)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start21 Nov 2018
- Primary completion11 Nov 2019
- Study completion11 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Klinik Valens
- Sponsor type
- University, hospital or other
- Collaborators
- German Sport University, Cologne
- Responsible party
- Principal investigator, Jens Bansi, Klinik Valens
- Investigators
- Jens Bansi, PhD, Principal investigator, Klinik Valens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03652519
- Sponsor's protocol ID
- BansiJ
- Acronym
- TRAINUVIMAB
- Status last verified
- Nov 2019
- First submitted
- 14 Aug 2018
- Last updated
- 13 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33782190Joisten 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.
PubMed 30849952
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03652519
- Acronym / sponsor ID
- TRAINUVIMAB / BansiJ
- Conditions
- Multiple Sclerosis
- Keywords
- Exercise, Immune Signalling, Cognition, Health-related Quality of Life
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Klinik ValensUniversity, hospital or other
- Collaborators
- German Sport University, Cologne
- Study start
- 21 Nov 2018 (actual)
- Primary completion
- 11 Nov 2019 (actual)
- Study completion
- 11 Nov 2019 (actual)
- First posted
- 29 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-intensity Interval Training (HIIT) | Experimental | Behavioral: Exercise TrainingParticipants of the HIIT group will exercise three times per week over a period of three weeks (inpatient rehabilitation) on a cycle ergometer. Exercise intensity will be regulated and heart rate controlled based on the achieved maximum heart rate (HRmax) assessed during the initial Cardiopulmonary Exercise Testing. Each exercise session will last 30 minutes and will be started and finalized with three minutes at low intensity (50% HRmax, warm-up / cool-down). During each exercise session, participants of the HIIT group will perform 5x one-and-a-half Minute high-intensive exercise bouts at 95-100% of their HRmax followed by active breaks of unloaded pedalling over 2 minutes with the aim to achieve 60% HRmax. |
| Moderate Continous Training (ST) | Active comparator | Behavioral: Exercise TrainingParticipants of the ST group will exercise three times per week over a period of three weeks (inpatient rehabilitation) on a cycle ergometer. Exercise intensity will be regulated and heart rate controlled based on the achieved maximum heart rate (HRmax) assessed during the initial Cardiopulmonary Exercise Testing. Each exercise session will last 30 minutes and will be started and finalized with three minutes at low intensity (50% HRmax, warm-up / cool-down). During each exercise session, participants of the ST group will exercise 30 minutes continuously at 65% of HRmax. This moderate continous training program represents the standard care at the local rehabilitation clinic. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise TrainingTreatment 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. | Behavioural | High-intensity Interval Training (HIIT), Moderate Continous Training (ST) |
Primary outcome
Tregs
Time frame: Three weeks (day 0 to day 21)
Proportion of regulatory T-cells with higher values indicating higher levels of Inflammation.
10 secondary outcomes
Immune status
Time frame: Three weeks (day 0 to day 21)
Soluble factors (cytokines, tryptophan metabolites, blood brain barrier markers)
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)
Time frame: Three weeks (day 0 to day 21)
Endurance capacity
Time frame: Three weeks (day 0 to day 21)
Assessment of Motor and Processing Skills (AMPS)
Time frame: Three weeks (day 0 to day 21)
Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
Time frame: Three weeks (day 0 to day 21)
Fatigue Scale of Motor and cognitive function (FSMC)
Time frame: Three weeks (day 0 to day 21)
Hospital Anxiety and Depression Scale (HADS)
Time frame: Three weeks (day 0 to day 21
Patient-Reported Outcome Measurement Information System (PROMIS)
Time frame: Three weeks (day 0 to day 21)
Test battery of attention (TAP)
Time frame: Three weeks (day 0 to day 21)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Derived from this study: PubMed 33782190Joisten 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.
- Derived from this study: PubMed 30849952Joisten 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Bansi, PhD principal investigator
Klinik Valens
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise Training in people with Multiple Sclerosis, run by Klinik Valens at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tregs (time frame: Three weeks (day 0 to day 21)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03652519, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019.