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Completed

NCT Number: NCT04191772

The Impact of Training on Sitting Time and Brain Volumes 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.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Behavior Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Motor Activity Nervous System Diseases Sedentary Behavior

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hasselt University

Diepenbeek, Limburg, 3590, Belgium

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Multiple Sclerosis according to the McDonald criteria (Relaps remitting)
  • Written informed consent
  • Medical safety screening

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Periodized, home-based running program

Other

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.

Primary outcomes

  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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).

  9. 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).

  10. 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).

  11. 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).

  12. 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).

  13. 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).

  14. 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).

  15. 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).

  16. 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).

  17. 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).

  18. 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).

  19. 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).

  20. 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).

Secondary outcomes

  1. Blood pressure

    Time frame: Baseline

    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.

  2. Blood pressure

    Time frame: Week 48 of the training program

    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.

  3. Resting heart rate

    Time frame: Baseline

    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.

  4. Resting heart rate

    Time frame: Week 48 of the training program

    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.

  5. Total calorie intake

    Time frame: Baseline

    Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.

  6. Total calorie intake

    Time frame: Week 12 of the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.

  7. Total calorie intake

    Time frame: Week 24 of the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.

  8. Total calorie intake

    Time frame: Week 48 of the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.

  9. Total calorie intake

    Time frame: 3 months after the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the total calorie intake is calculated.

  10. Macronutrient content

    Time frame: Baseline

    Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.

  11. Macronutrient content

    Time frame: Week 12 of the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.

  12. Macronutrient content

    Time frame: Week 24 of the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.

  13. Macronutrient content

    Time frame: Week 48 of the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.

  14. Macronutrient content

    Time frame: 3 months after the training program

    Participants will record all food and beverages consumed over seven consecutive days and from this the macronutrient content is calculated.

  15. Participation - Ghent Participation Scale (GPS)

    Time frame: Baseline

    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.

  16. Participation - Ghent Participation Scale (GPS)

    Time frame: Week 48 of the training program

    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.

  17. Mobility - MS walking scale (MSWS-12)

    Time frame: Baseline

    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

  18. Mobility - MS walking scale (MSWS-12)

    Time frame: Week 48 of the training program

    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

  19. Fatigue - Modified Fatigue Impact scale (MFIS)

    Time frame: Before start of the intervention

    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.

  20. Fatigue - Modified Fatigue Impact scale (MFIS)

    Time frame: Week 1 of the intervention

    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.

  21. Fatigue - Modified Fatigue Impact scale (MFIS)

    Time frame: Week 12 of the training program

    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.

  22. Fatigue - Modified Fatigue Impact scale (MFIS)

    Time frame: Week 24 of the training program

    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.

  23. Fatigue - Modified Fatigue Impact scale (MFIS)

    Time frame: Week 48 of the training program

    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.

  24. Fatigue - Modified Fatigue Impact scale (MFIS)

    Time frame: 3 months after the training program

    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.

  25. Cognition - Spatial Recall test (SPART)

    Time frame: Baseline

    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

  26. Cognition - Spatial Recall test (SPART)

    Time frame: Week 48 of the training program

    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

  27. Cognition - Symbol Digit Modalities Test (SDMT)

    Time frame: Baseline

    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.

  28. Cognition - Symbol Digit Modalities Test (SDMT)

    Time frame: Week 48 of the training program

    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.

  29. Body weight

    Time frame: Baseline

    Body weight is determined using a digital-balanced weighting scale to the nearest 0.1kg

  30. Body weight

    Time frame: Week 48 of the training program

    Body weight is determined using a digital-balanced weighting scale to the nearest 0.1kg

  31. Height

    Time frame: Baseline

    Body height is measured to the nearest 0.1cm using a wall-mounted Harpenden stadiometer, with participants barefoot

  32. Height

    Time frame: Week 48 of the training program

    Body height is measured to the nearest 0.1cm using a wall-mounted Harpenden stadiometer, with participants barefoot

  33. DEXA (Dual Energy X-Ray)

    Time frame: Baseline

    body fat mass and lean tissue mass using Dual Energy X-ray Absorptiometry

  34. DEXA (Dual Energy X-Ray)

    Time frame: Week 48 of the training program

    body fat mass and lean tissue mass using Dual Energy X-ray Absorptiometry

  35. Coordination - timed tandem walk (TTW)

    Time frame: Baseline

    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.

  36. Coordination - timed tandem walk (TTW)

    Time frame: Week 48 of the training program

    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.

  37. Oxygen uptake (VO2)

    Time frame: Baseline

    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.

  38. Oxygen uptake (VO2)

    Time frame: Week 48 of the training program

    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.

  39. Carbon dioxide output (VCO2)

    Time frame: Baseline

    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.

  40. Carbon dioxide output (VCO2)

    Time frame: Week 48 of the training protocol

    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.

  41. Minute ventilation (VE)

    Time frame: Baseline

    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.

  42. Minute ventilation (VE)

    Time frame: Week 48 of the training protocol

    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.

  43. Equivalents for oxygen uptake (VE/VO2)

    Time frame: Baseline

    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.

  44. Equivalents for oxygen uptake (VE/VO2)

    Time frame: Week 48 of the training protocol

    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.

  45. Equivalents for carbon dioxide production (VE/VCO2)

    Time frame: Baseline

    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.

  46. Equivalents for carbon dioxide production (VE/VCO2)

    Time frame: Week 48 of the training program

    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.

  47. Tidal volume (Vt)

    Time frame: Baseline

    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.

  48. Tidal volume (Vt)

    Time frame: Week 48 of the training program

    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.

  49. Breathing frequency (BF)

    Time frame: Baseline

    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.

  50. Breathing frequency (BF)

    Time frame: Week 48 of the training protocol

    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.

  51. Respiratory gas exchange ratio (RER)

    Time frame: Baseline

    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.

  52. Respiratory gas exchange ratio (RER)

    Time frame: Week 48 of the training program

    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.

  53. Cardiorespiratory fitness (CRF)

    Time frame: Baseline

    CRF will be measured with a maximal cardiopulmonary exercise test on a bicycle ergometer.

  54. Cardiorespiratory fitness (CRF)

    Time frame: Week 48 of the training program

    CRF will be measured with a maximal cardiopulmonary exercise test on a bicycle ergometer.

  55. Lipidomic profile

    Time frame: Baseline

    Blood analysis

  56. Lipidomic profile

    Time frame: Week 48 of the training program

    Blood analysis

  57. Brain volumes

    Time frame: Baseline

    MRI scan

  58. Brain volumes

    Time frame: Week 48 of the training program

    MRI scan

  59. PBMC subset parameters

    Time frame: Baseline

    flow cytometry analysis of immune cell subsets in peripheral blood-derived mononuclear cells (PBMCs)

  60. PBMC subset parameters

    Time frame: Week 48 of the training program

    flow cytometry analysis of immune cell subsets in peripheral blood-derived mononuclear cells (PBMCs)

  61. serum cytokines

    Time frame: Baseline

    cytokine levels are measured by ELISA on serum derived from peripheral blood samples

  62. serum cytokines

    Time frame: Week 48 of the training program

    cytokine levels are measured by ELISA on serum derived from peripheral blood samples

Sponsors and collaborators

Lead sponsor

Hasselt University

Other

Registry information

Official study title

The Impact of Structured Exercise on Physical Fitness, Sedentary Time, Brain Volume, Cognitive, Health-related and Immunological Parameters in Multiple Sclerosis.

Acronym: EXIMS

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Dec 10, 2019
Registry last updated
Aug 31, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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