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High-intensity Training and Its Effects on Neuroplasticity (TRAINUVIMAB)

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Exercise Training
Sponsored by
Klinik Valens
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Multiple Sclerosis focused on measuring Exercise, Immune Signalling, Cognition, Health-related Quality of Life

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kliniken-Valens

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

High-intensity Interval Training (HIIT)

Moderate Continous Training (ST)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Tregs
Proportion of regulatory T-cells with higher values indicating higher levels of Inflammation.

Secondary Outcome Measures

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.
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.
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.
Endurance capacity
Endurance capacity will be measured by peak oxygen consumption achieved in the cardiopulmonary exercise test. Higher values indicate better cardiorespiratory fitness.
Assessment of Motor and Processing Skills (AMPS)
Processing skills of executive functions
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.
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.
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.
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.
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.

Full Information

First Posted
August 14, 2018
Last Updated
November 11, 2019
Sponsor
Klinik Valens
Collaborators
German Sport University, Cologne
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1. Study Identification

Unique Protocol Identification Number
NCT03652519
Brief Title
High-intensity Training and Its Effects on Neuroplasticity
Acronym
TRAINUVIMAB
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

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
November 21, 2018 (Actual)
Primary Completion Date
November 11, 2019 (Actual)
Study Completion Date
November 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Klinik Valens
Collaborators
German Sport University, Cologne

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Exercise, Immune Signalling, Cognition, Health-related Quality of Life

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High-intensity Interval Training (HIIT)
Arm Type
Experimental
Arm Description
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.
Arm Title
Moderate Continous Training (ST)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Exercise Training
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tregs
Description
Proportion of regulatory T-cells with higher values indicating higher levels of Inflammation.
Time Frame
Three weeks (day 0 to day 21)
Secondary Outcome Measure Information:
Title
Immune status
Description
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)
Title
Soluble factors (cytokines, tryptophan metabolites, blood brain barrier markers)
Description
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)
Title
Migratory Potential of peripheral mononuclear cells (PBMC)
Description
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)
Title
Endurance capacity
Description
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)
Title
Assessment of Motor and Processing Skills (AMPS)
Description
Processing skills of executive functions
Time Frame
Three weeks (day 0 to day 21)
Title
Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
Description
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)
Title
Fatigue Scale of Motor and cognitive function (FSMC)
Description
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)
Title
Hospital Anxiety and Depression Scale (HADS)
Description
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
Title
Patient-Reported Outcome Measurement Information System (PROMIS)
Description
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)
Title
Test battery of attention (TAP)
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Bansi, PhD
Organizational Affiliation
Klinik Valens
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kliniken-Valens
City
Valens
State/Province
Sankt Gallen
ZIP/Postal Code
7317
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33782190
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.
Results Reference
derived
PubMed Identifier
30849952
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.
Results Reference
derived

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High-intensity Training and Its Effects on Neuroplasticity

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