Project R-16390

A multi-modal, tailored and adaptive exercise program to improvewalking capacity in persons with progressive MS and abnormalfatigability (Research)

The POTENTIAL (POTential in people with progressive multiple sclerosis to ENhance walking capacity Through Intensive and individually-Adapted Locomotor exercise) trial is a randomized, double-blind, multicenter study evaluating exercise-based rehabilitation strategies for people with progressive multiple sclerosis (MS) experiencing walking-related fatigability and mobility limitations. The study compares a personalized, high-intensity multimodal exercise intervention with a standardized low-intensity exercise program to determine their effects on walking endurance and mobility outcomes. Walking fatigability is a major contributor to reduced independence and quality of life in progressive MS, particularly in individuals with moderate-to-severe disability. Existing rehabilitation approaches often provide limited benefits in this population. The intervention evaluated in POTENTIAL combines intermittent walking training with tailored complementary exercise modules targeting functions such as balance, agility, and lower-limb movement control. Treatment is individualized according to participant characteristics and reassessed during the program to allow adaptation over time. The trial builds on promising pilot work demonstrating feasibility, safety, acceptability, and preliminary improvements in walking endurance and gait-related outcomes. A total of 148 participants will be recruited across six MS expert centers in five countries and randomly assigned to one of the two exercise interventions delivered over 12 weeks. Assessments will be conducted at multiple time points up to 24 weeks. Primary and secondary outcomes include measures of walking endurance, gait quality, fatigue impact, balance, mobility, patient-reported outcomes, and real-life walking performance using wearable technology. The study also evaluates intervention fidelity, safety, and participant perspectives. Developed with strong stakeholder involvement, including people living with progressive MS, the POTENTIAL trial aims to generate evidence for scalable and personalized rehabilitation strategies that can improve mobility and reduce fatigability in progressive MS, while informing future clinical rehabilitation practice.

01 February 2026 - 31 January 2030