Measuring the Effects of the Commonest Exercise Programs on Subjective Fatigue in People with Multiple Sclerosis: A Randomized Effectiveness Trial

Purpose: To test and compare the effects of the four most common exercise-based interventions employed to manage subjective fatigue and functional impairments due to multiple sclerosis (MS). Methods: Persons with MS (PwMS) complaining of fatigue as main symptom were enrolled. After a comprehensive baseline assessment evaluating subjective fatigue impact and severity (primary endpoints), quality of life, cardiorespiratory performance and mobility and motor-functional outcomes, participants were randomly assigned to an eight-week intervention consisting of strength (ST) or aerobic training (AT) or strength+aerobic (Combo) or global rehabilitation (Rehab). Results: Sixty-two mildly-moderately disabled PwMS (median EDSS 3.5±1.6; age 46.6±11.8 years; 75% women) completed the study. No adverse events were reported. Between-group comparisons did not detect significant differences among groups. Considering training-induced effects separately for each group, AT showed the largest reduction in the Fatigue Severity Score (-18.8%; -0.81 pts, CI: -1.53, -0.09, p=0.03) followed by ST (-16.8%; -0.84 pts, IC: -1.56, -0.12, p=0.02). Fatigue impact assessed by MFIS was significantly reduced after AT (-35.3%; -12.44 pts, CI: -19.00, -5.87, p<0.01), followed by Combo (-33.8%; -13.36 pts; CI: -20.38, -6.34, p<0.01) and Rehab (-26.2%; -8.18 pts; CI: -16.10, -0.26, p=0.04). Regarding motor-functional outcomes, beyond the expected training-specific effects (e.g., muscle strength gains following ST, increased cardiorespiratory fitness following AT), comfortable and fastest walking speed increased significantly following Rehab (+0.16 m·s -1, CI: 0.08, 0.23, p<0.01; +0.22 m·s -1, CI: 0.11, 0.329, p<0.01, respectively) exceeding established thresholds for clinically important changes. Also the increased distance covered in six minutes was found to exceed clinically importance thresholds following ST (+55 m, CI: 9.15, 101.02, p=0.02) and Combo (+62 m, CI: 14.04, 109.13, p=0.01). Conclusions: Although the superiority of one treatment over the others has yet to be claimed and all interventions proved beneficial to reduce fatigue impact, only AT and ST reduced both fatigue severity and impact, with the former intervention associated with the largest within-group effect sizes. When testing the effects of interventions on mobility outcomes, AT led to the largest improvements, followed by Combo.