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Background  Persons with multiple sclerosis (PwMS) often have reduced aerobic capacity and report fatigue as the most disabling symptom impacting their health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for successful management of symptoms, although there is little supporting evidence. The aim of this study is to evaluate the effect of a multimodal therapy approach, including endurance training and patient education, during a three-week inpatient rehabilitation stay, on HRQoL in PwMS at six months follow-up. Inpatient energy management education (IEME) + high-intensity interval training (HIIT) will be compared with progressive muscle relaxation (PMR) + moderate continuous training (MCT).    Methods  This study has a two-armed single-blind randomized controlled superiority trial design. One hundred six PwMS-related fatigue (relapsing-remitting or chronic progressive phenotypes; Expanded Disability Status Scale (EDSS) ≤ 6.5) will be recruited at the Valens clinic, Switzerland, and randomized into either an experimental (EG) or a control group (CG). EG: participants will perform IEME twice and HIIT three times per week during the three-week rehabilitation stay. IEME is a group-based intervention, lasting for 6.5 h over three weeks. HIIT contains of five 1.5-min high-intensive exercise bouts on a cycle ergometer at 95–100% of peak heart rate (HR peak ), followed by active breaks of unloaded pedalling for 2 min to achieve 60% of HR peak . CG: participants will perform PMR twice and MCT three times per week during the three-week rehabilitation stay, representing local usual care. PMR consists of six 1-h relaxation group sessions. MCT consists of 24-min continuous cycling at 65% of HR peak . The primary outcome is HRQoL (Physical and Mental Component Summaries of the Medical Outcome Study 36-item Short Form Health Survey; SF-36), measured at entry to the clinic (baseline, T 0 ), three weeks after T 0  (T 1 ) and at four (T 2 ) and six (T 3 ) months after T 0 . Secondary outcomes comprise cardiorespiratory fitness, inflammatory markers (measured at T 0  and T 1 ), fatigue, mood, self-efficacy, occupational performance, physical activity (measured at T 0 , T 1 , T 2  and T 3 ) and behaviour changes in energy management (measured at T 2  and T 3 ).    Discussion  This study will provide detailed information on a multimodal therapy approach to further improve rehabilitation for PwMS.    Trial registration  This trial was prospectively registered at ClinicalTrials.gov ( NCT04356248 ; 22 April 2020).    Supplementary Information  The online version contains supplementary material available at 10.1186/s12883-021-02084-0.

bmc neurology

High-intensity interval training and energy management education, compared with moderate continuous training and progressive muscle relaxation, for improving health-related quality of life in persons with multiple sclerosis: study protocol of a randomized controlled superiority trial with six months’ follow-up