Multiple SclerosisEXIMSNCT04191772
The Impact of Training on Sitting Time and Brain Volumes in Multiple Sclerosis.
A study testing Periodized, home-based running program in people with Multiple Sclerosis, run by Hasselt University at 1 site in Belgium.
Trial summary
The current study aims to investigate whether persons with Multiple Sclerosis (PwMS) compensate training time with more sedentary time and consequently blunt training effects. The second aim will be to investigate the effect of a structured training program on specific brain volumes and cognitive variables. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Periodized, home-based running program
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteBelgium
- Study dates
- 15 Jan 2020to 30 Jun 2021
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Multiple Sclerosis according to the McDonald criteria (Relaps remitting)
- Written informed consent
- Medical safety screening
Who cannot join
- Contra-indications to participate in moderate to high intensity exercise
- Contra-indications to undergo magnetic resonance imaging (pacemaker/defibrillator or wires other than sternal wires, insulin pumps, metal foreign bodies, deep brain stimulator, cerebral aneurysm clips, cochlear implant, magnetic dental implant, drug infusion device)
- Medication changes in the last month before the start of the intervention
- Following or plan to follow a weight reduction program
- Pregnancy
- Participation in another study
Show all 10Show fewer
- Acute MS exacerbation < 3 months prior to the start of the study
- EDSS score > 4
- Consumption of more than 20 alcohol units/week
- No daily internet access
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Impact of Structured Exercise on Physical Fitness, Sedentary Time, Brain Volume, Cognitive, Health-related and Immunological Parameters in Multiple Sclerosis.
The current study aims to investigate whether persons with Multiple Sclerosis (PwMS) compensate training time with more sedentary time and consequently blunt training effects. The second aim will be to investigate the effect of a structured training program on specific brain volumes and cognitive variables.
Read the detailed description
Multiple Sclerosis is a progressive, autoimmune, neurodegenerative disorder of the central nervous system (CNS) that predominantly affects young to middle-aged adults. It is characterized by a chronic inflammatory process that causes demyelination, axonal damage and white matter lesions across the CNS. Furthermore, evidence also indicates grey matter (GM) atrophy which has been reported to be significantly correlated with both clinical and cognitive deterioration. Clinical manifestations include spasticity, tremor, paralysis, walking difficulties and cognitive abnormalities. Due to these primary disease symptoms, persons with MS (PwMS) appear to be susceptible to a sedentary lifestyle and inactivity, which consequently increases the risk of other important, health-related secondary deficits including respiratory, metabolic and cardiac dysfunction. These deficits further contribute to a decrease in cardiorespiratory fitness and quality of life (QoL), thereby causing a vicious circle of decreased exercise tolerance, greater disability and increased inactivity. Since pharmacological treatment has little impact on these secondary deficits, exercise therapy has become an important aspect of the treatment of MS.
Hence, exercise therapy interventions in MS have been studied extensively and have already been proven to significantly improve cardiorespiratory fitness, muscle strength, balance, fatigue, cognition, quality of life, respiratory function and brain volumes. Moreover, a dose-response relationship has been reported for functional variables such as strength and endurance capacity. As such, high intensity interval training (HIIT) probably is exerts superior effects compared to traditional low/moderate intensity continuous training (MICT). However and in contrast with other populations, effects of HIIT on important health-related variables such as body composition, blood pressure and blood lipid profiles are less evident. Possibly, PwMS do not reach the exercise intensities required to improve such factors due to cardiovascular autonomic dysfunction, leading to impaired carotid baroreflex control, attenuated elevations in blood pressure and disturbed increases in heart rate, and abnormal muscle energy metabolism. Moreover, higher intensities might hamper longer-term implementation in real life, as an inverse relation between exercise intensity and training adherence has already been reported.
Training periodization (alternating HIIT and MICT) offers a solution to overcome the barrier of adherence and concurrently augmenting training effects, but in contrast to other populations, the addition of a lower intensity training component does still not improve health-related variables. Therefore, other approaches are warranted. Recently, evidence is growing that sedentary time is an important health risk factor, independent of the (dis)practice of structured exercise. Hence, PwMS possibly compensate training effects with even more sedentary time, in addition to an already sedentary lifestyle as mentioned previously. As such, addressing sedentary time might be an interesting new approach to counteract the health-related deficits in PwMS. Therefore, the present study explores the impact of a structured exercise program on sedentary time and health-related variables.
Furthermore, a secondary aim of the current project is to investigate the effect of a periodized training program on brain volumes and cognitive function. Recent evidence of physical training effects on cognitive variables is contradictory. So for exercise intervention studies that studied the latter only used short-term and laboratory-based training programs and included exercise modalities (type, intensity, duration) that are difficult to compare. Interestingly, a recent short-term randomized controlled trial reported superior effects of HIIT on cognitive functions compared to MICT. Hence, the current study aims to investigate the impact of a long-term, home-based training program with HIIT-components on cognitive variables.
- Conditions
- Multiple Sclerosis
- Being tested
- Periodized, home-based running program
- Keywords
- Sedentary time, Exercise, Brain volume, Health-related variables, Immunological variables, Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis, Sedentary Behavior, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Periodized, home-based running programOther
All participants will perform a home-based supervised exercise training program. Participants will receive weekly training instructions using a smartphone-based heart rate monitor application (Polar® app). Training sessions will involve running and the design of the training program will be based on linear periodization, where aerobic capacity is built firstly through a period of high-volume/low-intensity training before the proportion of high-intensity training is increased. The total duration of the exercise program will be 12 months with three weekly training sessions. Training progression will be dependent on initial VO2max values and running experience. VO2max classification is based on reference values described in V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics.
| Study group | Role | What they receive |
|---|---|---|
| MS - training goal 1 | Experimental | Persons with Multiple Sclerosis (PwMS) with a 'poor VO2max', a 'fair VO2max' with no running experience and a 'good VO2max' with no running experience (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the first training group will be trained to run continuously for 45 minutes. Receives: Other: Periodized, home-based running program |
| HC - training goal 1 | Experimental | Healthy control (HC) persons with a 'poor VO2max', a 'fair VO2max' with no running experience and a 'good VO2max' with no running experience (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the first training group will be trained to run continuously for 45 minutes. Receives: Other: Periodized, home-based running program |
| MS - training goal 2 | Experimental | PwMS with a 'fair VO2max' and running experience, a 'good VO2max and running experience', an 'excellent VO2max' and a 'superior VO2max' (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the second training group will be trained to run continuously for 75 minutes. Receives: Other: Periodized, home-based running program |
| HC - training goal 2 | Experimental | HC with a 'fair VO2max' and running experience, a 'good VO2max and running experience', an 'excellent VO2max' and a 'superior VO2max' (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the second training group will be trained to run continuously for 75 minutes. Receives: Other: Periodized, home-based running program |
| MS - sedentary control group | No intervention | Twenty PwMS will receive no intervention, only usual care. |
| HC - sedentary control group | No intervention | Twenty HC will receive no intervention, only usual care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of steps per day
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Before start of the training program
Number of steps per day
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 1 of the training program
Number of steps per day
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 24 of the training program
Number of steps per day
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 48 of the training program
Number of steps per day
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: 3 months after the training program
Sitting time
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Before start of the training program
Sitting time
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 1 of the training program
Sitting time
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 24 of the training program
Sitting time
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 48 of the training program
Sitting time
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: 3 months after the training program
Standing time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Before start of the training program
Standing time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 1 of the training program
Standing time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 24 of the training program
Standing time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 48 of the training program
Standing time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: 3 months after the training program
Stepping time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Before start of the training program
Stepping time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 1 of the training program
Stepping time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 24 of the training program
Stepping time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: Week 48 of the training program
Stepping time
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Measured: 3 months after the training program
Secondary outcomes (62)
Blood pressure
Systolic, diastolic and mean arterial blood pressure will be measured 4 times at 5-min intervals after an initial resting period of 10min, using an electronic sphygmomanometer (Omron®, Omron Healthcare, IL, USA) from the dominant arm and documented as the mean value of the final 3 measurements.
Measured: Baseline
Blood pressure
Systolic, diastolic and mean arterial blood pressure will be measured 4 times at 5-min intervals after an initial resting period of 10min, using an electronic sphygmomanometer (Omron®, Omron Healthcare, IL, USA) from the dominant arm and documented as the mean value of the final 3 measurements.
Measured: Week 48 of the training program
Resting heart rate
Resting heart rate will be measured 4 times at 5-min intervals after an initial resting period of 10min, using an electronic sphygmomanometer (Omron®, Omron Healthcare, IL, USA) from the dominant arm and documented as the mean value of the final 3 measurements.
Measured: Baseline
Resting heart rate
Resting heart rate will be measured 4 times at 5-min intervals after an initial resting period of 10min, using an electronic sphygmomanometer (Omron®, Omron Healthcare, IL, USA) from the dominant arm and documented as the mean value of the final 3 measurements.
Measured: Week 48 of the training program
Total calorie intake
Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.
Measured: Baseline
Total calorie intake
Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.
Measured: Week 12 of the training program
Total calorie intake
Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.
Measured: Week 24 of the training program
Total calorie intake
Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.
Measured: Week 48 of the training program
Total calorie intake
Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.
Measured: 3 months after the training program
Macronutrient content
Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.
Measured: Baseline
Macronutrient content
Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.
Measured: Week 12 of the training program
Macronutrient content
Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.
Measured: Week 24 of the training program
Macronutrient content
Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.
Measured: Week 48 of the training program
Macronutrient content
Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.
Measured: 3 months after the training program
Participation - Ghent Participation Scale (GPS)
The GPS is a generic instrument including both objective and all relevant subjective variables resulting in one score, already proven to be valid to rate participation in MS.
Measured: Baseline
Participation - Ghent Participation Scale (GPS)
The GPS is a generic instrument including both objective and all relevant subjective variables resulting in one score, already proven to be valid to rate participation in MS.
Measured: Week 48 of the training program
Mobility - MS walking scale (MSWS-12)
The MSWS-12 is a 12-item self-assessment scale which measures the impact of MS on mobility, which showed the ability of a running program to reduce impact of MS on walking ability in a previous pilot RCT by our research group
Measured: Baseline
Mobility - MS walking scale (MSWS-12)
The MSWS-12 is a 12-item self-assessment scale which measures the impact of MS on mobility, which showed the ability of a running program to reduce impact of MS on walking ability in a previous pilot RCT by our research group
Measured: Week 48 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
To evaluate the impact of structured training on fatigue, the Modified Fatigue Impact Scale (MFIS) will be used, which is the recommended questionnaire for research related to fatigue by the Multiple Sclerosis Council for Clinical guidelines. In the MFIS, the perceived impact of fatigue on physical, cognitive and psychosocial functioning of the past 4 weeks is assessed.
Measured: Before start of the intervention
Fatigue - Modified Fatigue Impact scale (MFIS)
To evaluate the impact of structured training on fatigue, the Modified Fatigue Impact Scale (MFIS) will be used, which is the recommended questionnaire for research related to fatigue by the Multiple Sclerosis Council for Clinical guidelines. In the MFIS, the perceived impact of fatigue on physical, cognitive and psychosocial functioning of the past 4 weeks is assessed.
Measured: Week 1 of the intervention
Fatigue - Modified Fatigue Impact scale (MFIS)
To evaluate the impact of structured training on fatigue, the Modified Fatigue Impact Scale (MFIS) will be used, which is the recommended questionnaire for research related to fatigue by the Multiple Sclerosis Council for Clinical guidelines. In the MFIS, the perceived impact of fatigue on physical, cognitive and psychosocial functioning of the past 4 weeks is assessed.
Measured: Week 12 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
To evaluate the impact of structured training on fatigue, the Modified Fatigue Impact Scale (MFIS) will be used, which is the recommended questionnaire for research related to fatigue by the Multiple Sclerosis Council for Clinical guidelines. In the MFIS, the perceived impact of fatigue on physical, cognitive and psychosocial functioning of the past 4 weeks is assessed.
Measured: Week 24 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
To evaluate the impact of structured training on fatigue, the Modified Fatigue Impact Scale (MFIS) will be used, which is the recommended questionnaire for research related to fatigue by the Multiple Sclerosis Council for Clinical guidelines. In the MFIS, the perceived impact of fatigue on physical, cognitive and psychosocial functioning of the past 4 weeks is assessed.
Measured: Week 48 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
To evaluate the impact of structured training on fatigue, the Modified Fatigue Impact Scale (MFIS) will be used, which is the recommended questionnaire for research related to fatigue by the Multiple Sclerosis Council for Clinical guidelines. In the MFIS, the perceived impact of fatigue on physical, cognitive and psychosocial functioning of the past 4 weeks is assessed.
Measured: 3 months after the training program
Cognition - Spatial Recall test (SPART)
The SPART is a visuospatial learning and delayed recall test, where a checkerboard with seven checkers in specified places is presented for 10sec to the participants who have to place the checkers back on a blank checkerboard immediately after and after another 30min. The total score is a sum of the correct checkers. This has been shown to be one of the most sensitive measures for detecting memory impairments in PwMS and showed improved performance after a running program in a previous pilot RCT of our research group
Measured: Baseline
Cognition - Spatial Recall test (SPART)
The SPART is a visuospatial learning and delayed recall test, where a checkerboard with seven checkers in specified places is presented for 10sec to the participants who have to place the checkers back on a blank checkerboard immediately after and after another 30min. The total score is a sum of the correct checkers. This has been shown to be one of the most sensitive measures for detecting memory impairments in PwMS and showed improved performance after a running program in a previous pilot RCT of our research group
Measured: Week 48 of the training program
Cognition - Symbol Digit Modalities Test (SDMT)
The SDMT is a test of information processing speed (PS) in which participants need to combine as many symbols with the accompanying numbers as possible in 90 seconds. The SDMT has been found to be a reliable and valid test in MS and a responder definition of approximating 4 points or 10% in magnitude SDMT change was recommended.
Measured: Baseline
Cognition - Symbol Digit Modalities Test (SDMT)
The SDMT is a test of information processing speed (PS) in which participants need to combine as many symbols with the accompanying numbers as possible in 90 seconds. The SDMT has been found to be a reliable and valid test in MS and a responder definition of approximating 4 points or 10% in magnitude SDMT change was recommended.
Measured: Week 48 of the training program
Body weight
Body weight is determined using a digital-balanced weighting scale to the nearest 0.1kg
Measured: Baseline
Body weight
Body weight is determined using a digital-balanced weighting scale to the nearest 0.1kg
Measured: Week 48 of the training program
Height
Body height is measured to the nearest 0.1cm using a wall-mounted Harpenden stadiometer, with participants barefoot
Measured: Baseline
Height
Body height is measured to the nearest 0.1cm using a wall-mounted Harpenden stadiometer, with participants barefoot
Measured: Week 48 of the training program
DEXA (Dual Energy X-Ray)
body fat mass and lean tissue mass using Dual Energy X-ray Absorptiometry
Measured: Baseline
DEXA (Dual Energy X-Ray)
body fat mass and lean tissue mass using Dual Energy X-ray Absorptiometry
Measured: Week 48 of the training program
Coordination - timed tandem walk (TTW)
Participants will have to walk in a straight line with one foot immediately in front of the other (heel to toe), while the arms are kept down at the side. Time to complete 3 meter will be monitored.
Measured: Baseline
Coordination - timed tandem walk (TTW)
Participants will have to walk in a straight line with one foot immediately in front of the other (heel to toe), while the arms are kept down at the side. Time to complete 3 meter will be monitored.
Measured: Week 48 of the training program
Oxygen uptake (VO2)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Oxygen uptake (VO2)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training program
Carbon dioxide output (VCO2)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VCO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Carbon dioxide output (VCO2)
Cardiopulmonary exercise test on on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VCO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training protocol
Minute ventilation (VE)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VE is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Minute ventilation (VE)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VE is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training protocol
Equivalents for oxygen uptake (VE/VO2)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VE/VO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Equivalents for oxygen uptake (VE/VO2)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VE/VO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training protocol
Equivalents for carbon dioxide production (VE/VCO2)
Cardiopulmonary exercise test on on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VE/VCO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Equivalents for carbon dioxide production (VE/VCO2)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis VE/VCO2 is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training program
Tidal volume (Vt)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis Vt is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Tidal volume (Vt)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis Vt is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training program
Breathing frequency (BF)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis BF is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Breathing frequency (BF)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis BF is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training protocol
Respiratory gas exchange ratio (RER)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis RER is collected breath-by-breath and averaged every ten seconds.
Measured: Baseline
Respiratory gas exchange ratio (RER)
Cardiopulmonary exercise test on a bicycle ergometer is performed. With the aid of continuous pulmonary gas exchange analysis RER is collected breath-by-breath and averaged every ten seconds.
Measured: Week 48 of the training program
Cardiorespiratory fitness (CRF)
CRF will be measured with a maximal cardiopulmonary exercise test on a bicycle ergometer.
Measured: Baseline
Cardiorespiratory fitness (CRF)
CRF will be measured with a maximal cardiopulmonary exercise test on a bicycle ergometer.
Measured: Week 48 of the training program
Lipidomic profile
Blood analysis
Measured: Baseline
Lipidomic profile
Blood analysis
Measured: Week 48 of the training program
Brain volumes
MRI scan
Measured: Baseline
Brain volumes
MRI scan
Measured: Week 48 of the training program
PBMC subset parameters
flow cytometry analysis of immune cell subsets in peripheral blood-derived mononuclear cells (PBMCs)
Measured: Baseline
PBMC subset parameters
flow cytometry analysis of immune cell subsets in peripheral blood-derived mononuclear cells (PBMCs)
Measured: Week 48 of the training program
serum cytokines
cytokine levels are measured by ELISA on serum derived from peripheral blood samples
Measured: Baseline
serum cytokines
cytokine levels are measured by ELISA on serum derived from peripheral blood samples
Measured: Week 48 of the training program
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start15 Jan 2020
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants will receive an intervention (exercise program) or no intervention (sedentary control group). Participants will be persons with MS and healthy controls.
- Masking
- None (open label)
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hasselt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bert Op't Eijnde, Hasselt University
- Investigators
- Bert Op 't Eijnde, Prof. dr., Study chair, Hasselt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04191772
- Sponsor's protocol ID
- EXIMS
- Acronym
- EXIMS
- Status last verified
- Aug 2021
- First submitted
- 5 Dec 2019
- Last updated
- 31 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nieste I, Spaas J, Franssen WMA, Asch PV, Savelberg HHCM, Eijnde BO. The effect of a structured running exercise intervention on non-exercise physical activity and sedentary behaviour in persons with mild Multiple Sclerosis and healthy controls. J Act Sedentary Sleep Behav. 2023 Dec 4;2(1):29. doi: 10.1186/s44167-023-00037-1.
PubMed 40217416
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Structured Exercise on Physical Fitness, Sedentary Time, Brain Volume, Cognitive, Health-related and Immunological Parameters in Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT04191772
- Acronym / sponsor ID
- EXIMS / EXIMS
- Conditions
- Multiple Sclerosis
- Keywords
- Sedentary time, Exercise, Brain volume, Health-related variables, Immunological variables, Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Hasselt UniversityUniversity, hospital or other
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 10 Dec 2019 (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.
The current study aims to investigate whether persons with Multiple Sclerosis (PwMS) compensate training time with more sedentary time and consequently blunt training effects. The second aim will be to investigate the effect of a structured training program on specific brain volumes and cognitive variables.
Detailed description
Multiple Sclerosis is a progressive, autoimmune, neurodegenerative disorder of the central nervous system (CNS) that predominantly affects young to middle-aged adults. It is characterized by a chronic inflammatory process that causes demyelination, axonal damage and white matter lesions across the CNS. Furthermore, evidence also indicates grey matter (GM) atrophy which has been reported to be significantly correlated with both clinical and cognitive deterioration. Clinical manifestations include spasticity, tremor, paralysis, walking difficulties and cognitive abnormalities. Due to these primary disease symptoms, persons with MS (PwMS) appear to be susceptible to a sedentary lifestyle and inactivity, which consequently increases the risk of other important, health-related secondary deficits including respiratory, metabolic and cardiac dysfunction. These deficits further contribute to a decrease in cardiorespiratory fitness and quality of life (QoL), thereby causing a vicious circle of decreased exercise tolerance, greater disability and increased inactivity. Since pharmacological treatment has little impact on these secondary deficits, exercise therapy has become an important aspect of the treatment of MS.
Hence, exercise therapy interventions in MS have been studied extensively and have already been proven to significantly improve cardiorespiratory fitness, muscle strength, balance, fatigue, cognition, quality of life, respiratory function and brain volumes. Moreover, a dose-response relationship has been reported for functional variables such as strength and endurance capacity. As such, high intensity interval training (HIIT) probably is exerts superior effects compared to traditional low/moderate intensity continuous training (MICT). However and in contrast with other populations, effects of HIIT on important health-related variables such as body composition, blood pressure and blood lipid profiles are less evident. Possibly, PwMS do not reach the exercise intensities required to improve such factors due to cardiovascular autonomic dysfunction, leading to impaired carotid baroreflex control, attenuated elevations in blood pressure and disturbed increases in heart rate, and abnormal muscle energy metabolism. Moreover, higher intensities might hamper longer-term implementation in real life, as an inverse relation between exercise intensity and training adherence has already been reported.
Training periodization (alternating HIIT and MICT) offers a solution to overcome the barrier of adherence and concurrently augmenting training effects, but in contrast to other populations, the addition of a lower intensity training component does still not improve health-related variables. Therefore, other approaches are warranted. Recently, evidence is growing that sedentary time is an important health risk factor, independent of the (dis)practice of structured exercise. Hence, PwMS possibly compensate training effects with even more sedentary time, in addition to an already sedentary lifestyle as mentioned previously. As such, addressing sedentary time might be an interesting new approach to counteract the health-related deficits in PwMS. Therefore, the present study explores the impact of a structured exercise program on sedentary time and health-related variables.
Furthermore, a secondary aim of the current project is to investigate the effect of a periodized training program on brain volumes and cognitive function. Recent evidence of physical training effects on cognitive variables is contradictory. So for exercise intervention studies that studied the latter only used short-term and laboratory-based training programs and included exercise modalities (type, intensity, duration) that are difficult to compare. Interestingly, a recent short-term randomized controlled trial reported superior effects of HIIT on cognitive functions compared to MICT. Hence, the current study aims to investigate the impact of a long-term, home-based training program with HIIT-components on cognitive variables.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Participants will receive an intervention (exercise program) or no intervention (sedentary control group). Participants will be persons with MS and healthy controls.
| Arm | Type | Receives |
|---|---|---|
| MS - training goal 1 | Experimental | Other: Periodized, home-based running programPersons with Multiple Sclerosis (PwMS) with a 'poor VO2max', a 'fair VO2max' with no running experience and a 'good VO2max' with no running experience (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the first training group will be trained to run continuously for 45 minutes. |
| HC - training goal 1 | Experimental | Other: Periodized, home-based running programHealthy control (HC) persons with a 'poor VO2max', a 'fair VO2max' with no running experience and a 'good VO2max' with no running experience (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the first training group will be trained to run continuously for 45 minutes. |
| MS - training goal 2 | Experimental | Other: Periodized, home-based running programPwMS with a 'fair VO2max' and running experience, a 'good VO2max and running experience', an 'excellent VO2max' and a 'superior VO2max' (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the second training group will be trained to run continuously for 75 minutes. |
| HC - training goal 2 | Experimental | Other: Periodized, home-based running programHC with a 'fair VO2max' and running experience, a 'good VO2max and running experience', an 'excellent VO2max' and a 'superior VO2max' (VO2max values according to V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics) will receive an exercise intervention existing of home-based running sessions. Participants of the second training group will be trained to run continuously for 75 minutes. |
| MS - sedentary control group | No intervention | –Twenty PwMS will receive no intervention, only usual care. |
| HC - sedentary control group | No intervention | –Twenty HC will receive no intervention, only usual care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Multiple Sclerosis according to the McDonald criteria (Relaps remitting)
- Written informed consent
- Medical safety screening
Key exclusion criteria (10 listed)
- Contra-indications to participate in moderate to high intensity exercise
- Contra-indications to undergo magnetic resonance imaging (pacemaker/defibrillator or wires other than sternal wires, insulin pumps, metal foreign bodies, deep brain stimulator, cerebral aneurysm clips, cochlear implant, magnetic dental implant, drug infusion device)
- Medication changes in the last month before the start of the intervention
- Following or plan to follow a weight reduction program
- Pregnancy
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 |
|---|---|---|
| Periodized, home-based running programAll participants will perform a home-based supervised exercise training program. Participants will receive weekly training instructions using a smartphone-based heart rate monitor application (Polar® app). Training sessions will involve running and the design of the training program will be based on linear periodization, where aerobic capacity is built firstly through a period of high-volume/low-intensity training before the proportion of high-intensity training is increased. The total duration of the exercise program will be 12 months with three weekly training sessions. Training progression will be dependent on initial VO2max values and running experience. VO2max classification is based on reference values described in V.H. Heyward, Advanced Fitness Assessment and Exercise Prescription, Fifth Edition, 2006, Champaign, IL: Human Kinetics. | Other | HC - training goal 1, HC - training goal 2, MS - training goal 1, MS - training goal 2 |
Primary outcome
Number of steps per day
Time frame: Before start of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Number of steps per day
Time frame: Week 1 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Number of steps per day
Time frame: Week 24 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Number of steps per day
Time frame: Week 48 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Number of steps per day
Time frame: 3 months after the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Sitting time
Time frame: Before start of the training program
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Sitting time
Time frame: Week 1 of the training program
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Sitting time
Time frame: Week 24 of the training program
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Sitting time
Time frame: Week 48 of the training program
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Sitting time
Time frame: 3 months after the training program
Sedentary behaviour will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Standing time
Time frame: Before start of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Standing time
Time frame: Week 1 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Standing time
Time frame: Week 24 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Standing time
Time frame: Week 48 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Standing time
Time frame: 3 months after the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Stepping time
Time frame: Before start of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Stepping time
Time frame: Week 1 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Stepping time
Time frame: Week 24 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Stepping time
Time frame: Week 48 of the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
Stepping time
Time frame: 3 months after the training program
Physical activity will be measured with the ActivPAL3TM activity monitor (PAL Technologies Ltd, Glasgow, UK).
62 secondary outcomes
Blood pressure
Time frame: Baseline
Blood pressure
Time frame: Week 48 of the training program
Resting heart rate
Time frame: Baseline
Resting heart rate
Time frame: Week 48 of the training program
Total calorie intake
Time frame: Baseline
Total calorie intake
Time frame: Week 12 of the training program
Total calorie intake
Time frame: Week 24 of the training program
Total calorie intake
Time frame: Week 48 of the training program
Total calorie intake
Time frame: 3 months after the training program
Macronutrient content
Time frame: Baseline
Macronutrient content
Time frame: Week 12 of the training program
Macronutrient content
Time frame: Week 24 of the training program
Macronutrient content
Time frame: Week 48 of the training program
Macronutrient content
Time frame: 3 months after the training program
Participation - Ghent Participation Scale (GPS)
Time frame: Baseline
Participation - Ghent Participation Scale (GPS)
Time frame: Week 48 of the training program
Mobility - MS walking scale (MSWS-12)
Time frame: Baseline
Mobility - MS walking scale (MSWS-12)
Time frame: Week 48 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
Time frame: Before start of the intervention
Fatigue - Modified Fatigue Impact scale (MFIS)
Time frame: Week 1 of the intervention
Fatigue - Modified Fatigue Impact scale (MFIS)
Time frame: Week 12 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
Time frame: Week 24 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
Time frame: Week 48 of the training program
Fatigue - Modified Fatigue Impact scale (MFIS)
Time frame: 3 months after the training program
Cognition - Spatial Recall test (SPART)
Time frame: Baseline
Cognition - Spatial Recall test (SPART)
Time frame: Week 48 of the training program
Cognition - Symbol Digit Modalities Test (SDMT)
Time frame: Baseline
Cognition - Symbol Digit Modalities Test (SDMT)
Time frame: Week 48 of the training program
Body weight
Time frame: Baseline
Body weight
Time frame: Week 48 of the training program
Height
Time frame: Baseline
Height
Time frame: Week 48 of the training program
DEXA (Dual Energy X-Ray)
Time frame: Baseline
DEXA (Dual Energy X-Ray)
Time frame: Week 48 of the training program
Coordination - timed tandem walk (TTW)
Time frame: Baseline
Coordination - timed tandem walk (TTW)
Time frame: Week 48 of the training program
Oxygen uptake (VO2)
Time frame: Baseline
Oxygen uptake (VO2)
Time frame: Week 48 of the training program
Carbon dioxide output (VCO2)
Time frame: Baseline
Carbon dioxide output (VCO2)
Time frame: Week 48 of the training protocol
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 31 Aug 2021.
- Derived from this study: PubMed 40217416Nieste I, Spaas J, Franssen WMA, Asch PV, Savelberg HHCM, Eijnde BO. The effect of a structured running exercise intervention on non-exercise physical activity and sedentary behaviour in persons with mild Multiple Sclerosis and healthy controls. J Act Sedentary Sleep Behav. 2023 Dec 4;2(1):29. doi: 10.1186/s44167-023-00037-1.
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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.
Bert Op 't Eijnde, Prof. dr. study chair
Hasselt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Periodized, home-based running program in people with Multiple Sclerosis, run by Hasselt University at 1 site in Belgium.
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 3 inclusion and 10 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 31 Aug 2021. 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 Belgium. 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?
Number of steps per day (time frame: Before start of the training program). The study lists 20 primary outcomes in all. 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 NCT04191772, which also lists 1 linked publication.
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 31 Aug 2021.