Abstract
BACKGROUND: Multimodal agility-based exercise training (MAT) is a group-based exercise training framework for persons with multiple sclerosis (pwMS) with a potential to impact fatigue and fatigability. In a mixed-methods design, this study evaluated the feasibility of implementing MAT in an inpatient rehabilitation setting and the feasibility of a randomized controlled trial (RCT) study protocol with 'traditional' strength and endurance training (SET) as an active control condition. Secondarily, preliminary outcome data was acquired. METHODS: PwMS with low to moderate disability and self-reported fatigue were randomly allocated to either MAT or SET when starting inpatient rehabilitation (4-6 weeks). The MAT-participants exercised in a group following a MAT-manual (sessions were gym- (5x/week) and pool-based (3x/week)). SET-participants exercised individually 5x/week on a cycle ergometer, and 3x/week on strength training machines. Feasibility assessments focused on processes, resources, management, time, and scientific domains. Assessed clinical outcomes at admission and discharge included perceived fatigue, motor and cognitive fatigability, cognitive performance, motor function, and balance confidence. Perceived fatigue was reassessed 1, 4, and 12 weeks after discharge. Feasibility was determined regarding predetermined progression criteria. RESULTS: Twenty-two participants were randomized. Both groups performed the minimum number of sessions (> 18), and retention was adequate (73-91%). SET-participants performed more sessions than MAT-participants (30.8 vs. 22.7) and stayed longer in the facility (34.2 vs. 31.6 days). Non-eligibility of admitted pwMS was high (74% non-eligible), mainly due to high EDSS and inability to attend pool-based sessions. Consequently, recruitment (1.8/month) was slower than the predetermined progression criterium. Baseline assessments took longer than required (only 50% completed within 3 days). Short-term fatigue reduction was similar for both groups. Motor fatigability also improved in both groups, whereas cognitive fatigability deteriorated. In MAT, average improvement in walking endurance (43.9 m) exceeded minimal important change values for individuals (> 26.9 m). CONCLUSIONS: Progressing to a definitive RCT necessitates adaptation of eligibility criteria. In the present design it will also be difficult to attain similar dosing of interventions. A multicenter RCT focused only on gym-based MAT might be another option to assess the effect of MAT. The primary outcome measure should be able to measure change in perceived fatigue more robustly. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00023943, date of registration: 23 September 2021.