A Phase 1 exercise dose escalation study for stroke survivors with impaired walking.

Background: Targeted exercise and increased practice can improve the mobility of stroke survivors. However, many stroke survivors continue to have reduced physical work capacity and impaired walking, and experience frequent falls after participating in physical rehabilitation programs.

Aim: In this Phase 1 study, we used a dose escalation method, common in pharmaceutical trials, to determine the maximum tolerable dose of multimodal exercise in community-dwelling stroke survivors with mobility impairment.

Methods: Stroke survivors 14-59 months poststroke participated in a 12-week (36 sessions) multimodal exercise program implemented using a cumulative 3 + 3 dose escalation design (featuring increasing doses in successive cohorts of three participants), with set dose-limiting tolerance criteria. The exercise intervention included challenging balance activities, strength, and endurance training. The program was individualized and focused on task-specific requirements for walking in the community.

Results: Six survivors participated before escalation was ceased. Four participants were able to tolerate up to 10·5 h/week of exercise, which included 283 min of endurance, 182 min of task practice, 138 min of strengthening, and 28 min resting. The program led to increased walking distance (Six-Minute Walk Test) and faster mobility (4 Square Step Test, Timed Up and Go Test), with pre-postimprovements averaging 23-41%.

Conclusions: This is the first multimodal exercise dose escalation study in stroke. The maximal dose of exercise identified was dramatically higher than the dose typically delivered to stroke survivors in current trials. We now plan to confirm safety and feasibility of this program in a larger Phase II trial.