Effects of inpatient energy management education and high-intensity interval training on health-related quality of life in persons with multiple sclerosis: A randomized controlled superiority trial with six-month follow-up

Background: Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (pwMS) and impacts health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for the treatment of fatigue in pwMS. However, high-quality evidence exists only for unimodal interventions, such as physical therapies/exercise or energy/fatigue management programmes. The primary objective of the current study was to test the hypothesis that a combination of inpatient energy management education (IEME) and high-intensity interval training (HIIT) is superior to a combination of progressive muscle relaxation (PMR) and moderate continuous training (MCT) for improving HRQoL at 6-month follow-up in fatigued pwMS. Methods: A randomized (1:1) controlled superiority trial with fatigued pwMS >18 years of age, with Expanded Disability Status Scale (EDSS) score <= 6.5, recruited at the Valens clinic, Switzerland. Participants in the experimental group performed IEME twice and HIIT 3 times per week and those in the usual care group performed PMR twice and MCT 3 times per week, during a 3-week inpatient rehabilitation stay. Primary outcome was HRQoL (Physical and Mental Component Scales of the Medical Outcome Study 36-item Short Form Health Survey (SF-36)), assessed at entry to the clinic (T-0), after 3 weeks' rehabilitation (T-1) and 4 (T-2) and 6 (T-3) months after T-0. Secondary outcomes included SF-36 subscales, fatigue (Fatigue Scale for Motor and Cognitive Functions (FSMC)), mood (Hospital Anxiety and Depression Scale (HADS)), self-efficacy for performing energy conservation strategies (Self-Efficacy for Performing Energy Conservation Strategies Assessment (SEPECSA)), self-perceived competence in activities of daily living (Occupational Self Assessment (OSA)) and cardiorespiratory fitness (peak oxygen consumption (V<(O)over dot>(2peak))). Data were analysed using a mixed model for repeated measures approach. Results: A total of 106 pwMS (age (years): 49.75 (9.87), 66% female, EDSS: 4.64 (1.32)) were recruited. There were no significant group x time interaction effects in the primary and secondary outcomes. There were significant between-group differences in the pairwise comparisons of the group x time interaction in favour of the IEME + HIIT group at: (i) T-1 in cardiorespiratory fitness (p = 0.011) and SEPECSA (p = 0.032); (ii) T-2 in SF-36 mental health subscale (p = 0.022), HADS anxiety subscale (p = 0.014) and SEPECSA (p = 0.040); (iii) T-3 in SF-36 physical functioning subscale (p = 0.012) and SEPECSA (p = 0.003). Conclusion: IEME + HIIT was not superior to PMR + MCT regarding the effects on HRQoL (SF-36 Physical and Mental Component Scales) at 6-month follow-up in pwMS. However, there were significant between-group differences in favour of IEME + HIIT in physical functioning and mental health (SF-36 subscales), anxiety (HADS), cardiorespiratory fitness (V<(O)over dot>(2peak)) and self-efficacy (SEPECSA) at different measurement time-points that need to be considered in clinical practice.