PROJECT SUMMARY / ABSTRACT Among the 7 million stroke survivors living in the U.S., fewer than 10% have adequate walking speed and endurance to complete normal daily activities like grocery shopping, which leads to a loss of life roles. Stroke rehabilitation guidelines recommend moderate-intensity aerobic training (MAT) via walking exercise to address this limitation in walking capacity. However, recent evidence suggests that MAT may have negligible effects among many people in the chronic phase of stroke (>6 months post stroke), especially those with severe gait impairment (speed <0.4 m/s). There is growing belief that a more vigorous training intensity (>60% heart rate reserve vs 40-60%) may be critical for eliciting greater improvements in walking capacity. Yet, the optimal training intensity has been difficult to determine among stroke survivors because neurologic impairments make it challenging to reach vigorous intensity. This study will use a novel training protocol to overcome this limitation. Based on the well-tested exercise science and cardiac rehabilitation strategy of high-intensity interval training (HIT), this protocol uses bursts of maximum speed walking alternating with recovery periods, to sustain higher intensities than physiologically possible with continuous exercise and with less perceived exertion. Preliminary results suggest that this innovative locomotor HIT protocol may improve walking capacity and other outcomes significantly more than MAT, and that it could be uniquely effective among patients with severe gait impairment, a subgroup that has not yet shown meaningful responses to MAT or other interventions. However, no previous studies have been large enough to test whether a more vigorous training program like HIT increases benefit more than risk, yields sustained gains in walking capacity beyond the end of training or elicits significantly greater improvement than moderate-intensity training among patients with severe gait impairment. In this study, 156 people at least 6 months post-stroke at 3 research sites across the U.S. will be randomized to perform either a HIT or MAT program, each involving 45 minutes of walking exercise with a physical therapist, 3 times per week for 12 weeks. Walking function, fatigue, aerobic capacity, and quality of life will be assessed by blinded raters at baseline, after 4, 8 and 12 weeks of training and 3 months after training ends, while safety will be monitored throughout. The primary statistical analysis will then determine which training intensity is better (vigorous or moderate) for safely producing meaningful and sustained improvements in walking capacity in chronic stroke. A second analysis will also assess whether vigorous training intensity is particularly critical for patients with severe gait impairment. At study completion, we expect to have gained foundational knowledge about how to select training intensity to maximize recovery of walking function after stroke. This new kn...