Clinical trial NCT04191772: The Impact of Training on Sitting Time and Brain Volumes in Multiple Sclerosis.
Official title: The Impact of Structured Exercise on Physical Fitness, Sedentary Time, Brain Volume, Cognitive, Health-related and Immunological Parameters in Multiple Sclerosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Sedentary time
Exercise
Brain volume
Health-related variables
Immunological variables
Multiple Sclerosis
Lead sponsor: Hasselt University
Sponsor class: OTHER
First posted: 2019-12-10
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will receive an intervention (exercise program) or no intervention (sedentary control group). Participants will be persons with MS and healthy controls.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of steps per day
timeFrame: Before start of the training program
measure: Number of steps per day
timeFrame: Week 1 of the training program
measure: Number of steps per day
timeFrame: Week 24 of the training program
measure: Number of steps per day
timeFrame: Week 48 of the training program
measure: Number of steps per day
timeFrame: 3 months after the training program
measure: Sitting time
timeFrame: Before start of the training program
measure: Sitting time
timeFrame: Week 1 of the training program
measure: Sitting time
timeFrame: Week 24 of the training program
measure: Sitting time
timeFrame: Week 48 of the training program
measure: Sitting time
timeFrame: 3 months after the training program
measure: Standing time
timeFrame: Before start of the training program
measure: Standing time
timeFrame: Week 1 of the training program
measure: Standing time
timeFrame: Week 24 of the training program
measure: Standing time
timeFrame: Week 48 of the training program
measure: Standing time
timeFrame: 3 months after the training program
measure: Stepping time
timeFrame: Before start of the training program
measure: Stepping time
timeFrame: Week 1 of the training program
measure: Stepping time
timeFrame: Week 24 of the training program
measure: Stepping time
timeFrame: Week 48 of the training program
measure: Stepping time
timeFrame: 3 months after the training program
Secondary outcomes:
measure: Blood pressure
timeFrame: Baseline
measure: Blood pressure
timeFrame: Week 48 of the training program
measure: Resting heart rate
timeFrame: Baseline
measure: Resting heart rate
timeFrame: Week 48 of the training program
measure: Total calorie intake
timeFrame: Baseline
measure: Total calorie intake
timeFrame: Week 12 of the training program
measure: Total calorie intake
timeFrame: Week 24 of the training program
measure: Total calorie intake
timeFrame: Week 48 of the training program
measure: Total calorie intake
timeFrame: 3 months after the training program
measure: Macronutrient content
timeFrame: Baseline
measure: Macronutrient content
timeFrame: Week 12 of the training program
measure: Macronutrient content
timeFrame: Week 24 of the training program
measure: Macronutrient content
timeFrame: Week 48 of the training program
measure: Macronutrient content
timeFrame: 3 months after the training program
measure: Participation - Ghent Participation Scale (GPS)
timeFrame: Baseline
measure: Participation - Ghent Participation Scale (GPS)
timeFrame: Week 48 of the training program
measure: Mobility - MS walking scale (MSWS-12)
timeFrame: Baseline
measure: Mobility - MS walking scale (MSWS-12)
timeFrame: Week 48 of the training program
measure: Fatigue - Modified Fatigue Impact scale (MFIS)
timeFrame: Before start of the intervention
measure: Fatigue - Modified Fatigue Impact scale (MFIS)
timeFrame: Week 1 of the intervention
measure: Fatigue - Modified Fatigue Impact scale (MFIS)
timeFrame: Week 12 of the training program
measure: Fatigue - Modified Fatigue Impact scale (MFIS)
timeFrame: Week 24 of the training program
measure: Fatigue - Modified Fatigue Impact scale (MFIS)
timeFrame: Week 48 of the training program
measure: Fatigue - Modified Fatigue Impact scale (MFIS)
timeFrame: 3 months after the training program
measure: Cognition - Spatial Recall test (SPART)
timeFrame: Baseline
measure: Cognition - Spatial Recall test (SPART)
timeFrame: Week 48 of the training program
measure: Cognition - Symbol Digit Modalities Test (SDMT)
timeFrame: Baseline
measure: Cognition - Symbol Digit Modalities Test (SDMT)
timeFrame: Week 48 of the training program
measure: Body weight
timeFrame: Baseline
measure: Body weight
timeFrame: Week 48 of the training program
measure: Height
timeFrame: Baseline
measure: Height
timeFrame: Week 48 of the training program
measure: DEXA (Dual Energy X-Ray)
timeFrame: Baseline
measure: DEXA (Dual Energy X-Ray)
timeFrame: Week 48 of the training program
measure: Coordination - timed tandem walk (TTW)
timeFrame: Baseline
measure: Coordination - timed tandem walk (TTW)
timeFrame: Week 48 of the training program
measure: Oxygen uptake (VO2)
timeFrame: Baseline
measure: Oxygen uptake (VO2)
timeFrame: Week 48 of the training program
measure: Carbon dioxide output (VCO2)
timeFrame: Baseline
measure: Carbon dioxide output (VCO2)
timeFrame: Week 48 of the training protocol
measure: Minute ventilation (VE)
timeFrame: Baseline
measure: Minute ventilation (VE)
timeFrame: Week 48 of the training protocol
measure: Equivalents for oxygen uptake (VE/VO2)
timeFrame: Baseline
measure: Equivalents for oxygen uptake (VE/VO2)
timeFrame: Week 48 of the training protocol
measure: Equivalents for carbon dioxide production (VE/VCO2)
timeFrame: Baseline
measure: Equivalents for carbon dioxide production (VE/VCO2)
timeFrame: Week 48 of the training program
measure: Tidal volume (Vt)
timeFrame: Baseline
measure: Tidal volume (Vt)
timeFrame: Week 48 of the training program
measure: Breathing frequency (BF)
timeFrame: Baseline
measure: Breathing frequency (BF)
timeFrame: Week 48 of the training protocol
measure: Respiratory gas exchange ratio (RER)
timeFrame: Baseline
measure: Respiratory gas exchange ratio (RER)
timeFrame: Week 48 of the training program
measure: Cardiorespiratory fitness (CRF)
timeFrame: Baseline
measure: Cardiorespiratory fitness (CRF)
timeFrame: Week 48 of the training program
measure: Lipidomic profile
timeFrame: Baseline
measure: Lipidomic profile
timeFrame: Week 48 of the training program
measure: Brain volumes
timeFrame: Baseline
measure: Brain volumes
timeFrame: Week 48 of the training program
measure: PBMC subset parameters
timeFrame: Baseline
measure: PBMC subset parameters
timeFrame: Week 48 of the training program
measure: serum cytokines
timeFrame: Baseline
measure: serum cytokines
timeFrame: Week 48 of the training program
Other outcomes:
Locations:
city: Diepenbeek
country: Belgium
facility: Hasselt University
state: Limburg
Study officials:
affiliation: Hasselt University
name: Bert Op 't Eijnde, Prof. dr.
role: STUDY_CHAIR
References: