Training and Energy Management Education to Improve Quality of Life in Persons With Multiple Sclerosis

Study Overview
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Brief Summary
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Persons with Multiple Sclerosis (PwMS) often suffer from impaired mobility and reduced aerobic capacity. Moreover, 65% of PwMS recognize fatigue as their most disabling symptom that quickly impacts patients' health-related quality of life (QoL). Systematic reviews that evaluate therapeutic options for MS-neurorehabilitation show good evidence for exercise and energy management/conservation programs to improve fatigue or its impact on daily life. Guidelines recommend a multidisciplinary approach but to date only unimodal interventions are investigated. This study aims to investigate the influence of the combination of two different therapeutic concepts: inpatient energy management education (IEME) + High-intensity interval training (HIIT). This intervention is compared with a control group that undergoes progressive muscle relaxation (PMR) + low-intensity training (ST). IEME or PMR is performed on two days (tue-thur) and HIIT or ST on three days (mo-wed-fr) / week. The primary outcome is the effect on the quality of life after three weeks rehabilitation and after returning home (at 4 and 6 months follow-up) in PwMS.

Official Title
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High Intensity Training and Energy Management Education vs. Standard Training and Muscle Relaxation, to Improve Quality of Life in Persons With Multiple Sclerosis, a Randomized Controlled Superiority Trial With Six Months' Follow-up

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Behavioral: Endurance Training
* Behavioral: Education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definite MS diagnosis (revised McDonald criteria, 2018). Age >18y Expanded Disability Status Scale (EDSS) score ≤ 6.5 Fatigue Scale of Motor and Cognitive function (FSMC) total score > 43 Literacy and understanding German Informed Consent Exclusion Criteria: Women who are pregnant or breastfeeding / have the intention to become pregnant during the course of the study Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.) Known or suspected non-compliance, drug or alcohol abuse Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Enrolment of the investigator, his/her family members, employees and other dependent persons Cognitive impairment Mini-Mental State Examination (MMSE) < 21 Major Depression or Hospital Anxiety and Depression Scale (HADS) >11 at baseline Stem cell treatment in the last 6 months Participation in a previous high-intensity interval training (HIIT) or inpatient energy management education (IEME) study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-intensity interval training + energy management education<br>High-intensity interval training (HIIT): physiologically defined heart rate-controlled cycling with 80-100 rounds per minute (rpm) at 95-100% of maximum heart rate (HRmax). Participants will perform 5 × 1.5-min high-intensive exercise bouts at 95-100% of their HRmax followed by active breaks of unloaded pedalling over 2 min with the aim to achieve 60% of HRmax. Energy management education (IEME): face-to-face education sessions of 6.5 h in duration over a 3-week period, all conducted by a trained occupational therapist. Participants acquire knowledge and understanding about factors that influence energy and the consequences of fatigue on their habits and lifestyle. Six weeks after returning home, the participants will receive a reinforcement letter in the form of information material to remember the content of the IEME and to reinforce the implementation of the behaviour change in managing energy. | Behavioral: Endurance Training<br>* Treatment in both arms consists of specific endurance exercise modalities (HIIT or ST). Treatments differ in the applied training intensities. Participants in both arms will exercise 3 times per week over a period of 3 weeks on a bicycle ergometer. Exercise sessions will be supervised by a trained physical therapist. Exercise intensity will be heart rate monitored based on the maximum heart rate (HRmax) assessed during the initial cardiopulmonary exercise test. Exercise sessions in both arms will include a warm-up and a cool-down period at low intensity (50% HRmax) for 3 min each.<br>Behavioral: Education<br>* Treatment in both arms consists of specific energy management education interventions (IEME or PMR). Treatments differ in the applied education approaches. Participants in both arms will exercise 2 times per week over a period of 3 weeks.<br>|
| Active Comparator: Low-intensity training + progressive muscle relaxation<br>Low-intensity training (ST): participants will exercise for 24 min continuously at 65% of participants' HRmax (60-70 rpm). Progressive muscle relaxation (PMR): The aim of PMR is to achieve enhanced mental relaxation by reducing muscle tension. Participants will attend six 1-h group sessions over the 3-week intervention period, instructed by a trained physical therapist. Six weeks after returning home, the participants will receive a reinforcement letter with information material for remembering the content of the PMR techniques and to reinforce the implementation of the exercises at home. | Behavioral: Endurance Training<br>* Treatment in both arms consists of specific endurance exercise modalities (HIIT or ST). Treatments differ in the applied training intensities. Participants in both arms will exercise 3 times per week over a period of 3 weeks on a bicycle ergometer. Exercise sessions will be supervised by a trained physical therapist. Exercise intensity will be heart rate monitored based on the maximum heart rate (HRmax) assessed during the initial cardiopulmonary exercise test. Exercise sessions in both arms will include a warm-up and a cool-down period at low intensity (50% HRmax) for 3 min each.<br>Behavioral: Education<br>* Treatment in both arms consists of specific energy management education interventions (IEME or PMR). Treatments differ in the applied education approaches. Participants in both arms will exercise 2 times per week over a period of 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-form 36 (SF-36) | Changes of health-related quality of life will be assessed with the SF-36. The SF-36 questionnaire comprises 36 items. Scores range from 0 to 100 with higher values indicating better QoL. | 6 months (day 0 - day 183) with time points set after three weeks (day 21) and 4 months (day 122). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Indicators of inflammatory activity | Soluble factors that are known to be produced or secreted in response to exercise and are suspected to modify immune homeostasis and blood brain barrier function through their inflammatory and anti-inflammatory properties. Changes of Matrix-metalloproteinases-2 (MMP-2), Tryptophan, Kynurenine, Kynurenine acid, Interferon-gamma (IFN-Gamma) and Interleukin-6 (IL-6) will be assessed. Higher values indicate higher levels of Inflammation. | Three weeks (day 0 - day 21). | 
| Cardiorespiratory Fitness | Changes of cardiorespiratory fitness will be measured by peak oxygen consumption achieved in the cardiopulmonary exercise test. Higher values indicate better cardiorespiratory fitness. | Three weeks (day 0 - day 21). | 
| Self-efficacy in performing energy conservation strategies (SEPECSA) | Changes of self-efficacy in performing energy conservation strategies will be assessed with a self-reported questionnaire. The questionnaire consists of 14 items. The participants are asked to rank how confident they are that they can perform each item on a scale from 1 (= not at all confident/sure) to 10 (= completely confident/sure). The final score is found by adding the total items' score and dividing it by 14, with higher scores indicating greater confidence in self-efficacy. | Six months (day 0 - day 183) with time points set after three weeks (day 21) and after 4 months (day 122). | 
| Self-perceived competence in activities of daily living (OSA) | Changes of self-perceived competence are assessed with a self reported questionnaire. The questionnaire consists of 21 items that represent participation in habits and roles, performance of skills, and volition for participation. Participants rate each item with two 4-point likert scales to indicate their self-perception of occupational competence (I have a lot of problems doing this - I have some difficulty doing this - I do this well - I do this extremely well) and value for importance (This is not so important to me - This is important to me - This is more important to me - This is most important to me). Following these two steps, clients review their ratings and choose areas of occupational performance and participation that they would like to change. Higher scores indicate better competences. | Six months (day 0 - day 21) with time points set after three weeks (day 21) and four months (day 122). | 
| Fatigue Scale of motor and cognitive function (FSMC) | Changes of motor and cognitive fatigue are assessed on a 5-point likert-scale. Max 50 Points for subscales, 100 Points for the Total score. Cut-off for fatigue is set for the total score at 43 and for the motoric and cognitive subscores at 22 with higher values participants being more fatigued. | Six months (day 0 - day 183) with time points set after three weeks (day 21) and four months (day 122). | 
| Hospital Anxiety and Depression Scale (HADS) | Changes of anxiety and depression over three weeks training on a 4-point likert scale scored 0-3. Max 21 Points for each subscale, cut off for anxiety and Depression are set at 7 Points higher values represent more anxiety and Depression. | 6 months (day 0 - day 183) with time points set after three weeks (day 21) and four months (day 122). |