ENhancing exercise with LIGHT to improve functioning in PAD: the ENLIGHTEN PAD Trial Walking exercise is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, walking exercise does not eliminate disability due to PAD. Even after completing one of our successful exercise interventions that meaningfully improved six-minute walk distance, 82% of 192 PAD participants still reported ischemic leg symptoms after the six-minute walk. Our LITE randomized trial of 305 people with PAD showed that, compared to a control group that did not exercise, home-based walking exercise that induced ischemic leg symptoms (i.e. high intensity) significantly improved six-minute walk, while home- based exercise that did not induce ischemic leg symptoms (i.e. low intensity) had no effect on six-minute walk. Despite greater benefits, ischemic leg symptoms during high intensity exercise reduced exercise adherence. We hypothesize that 670 nm light therapy, administered before home-based walking exercise, will increase minutes of high intensity exercise and enhance the benefits of exercise in PAD. Nitric oxide (NO) is an endogenous signaling molecule with therapeutic properties that improve limb perfusion and reverses the skeletal muscle pathology present in PAD. 670 nm light treatment of the lower extremities increases plasma nitrosothiols, a major source of NO activity. In our preliminary study, 670 nm light treatment of the legs acutely increased lower extremity arterial flow and six-minute walk distance in people with PAD. Therefore, we hypothesize that 670 nm light treatment of the legs immediately before walking exercise sessions will acutely increase nitrosothiols and NO and facilitate greater exercise intensity, thereby enhancing the chronic benefits of exercise in people with PAD. The ENLIGHTEN PAD Trial will collect preliminary data to test whether, in people with PAD, daily 670 nm light treatment of the lower extremities immediately before home-based walking exercise sessions improves six-minute walk distance at 4-month follow-up, compared to sham light. In primary aim #1, we will test whether 670 nm light + home-based exercise increases six-minute walk distance more than sham light + home-based exercise at 4-month follow-up. In primary aim #2, we will measure the acute effect of the first treatment of 670 nm light on six-minute walk distance and on walking intensity (measured with the ActiGraph accelerometer) during the six-minute walk. In secondary and exploratory aims, we will delineate biologic pathways by which 670 nm light enhances the benefits of walking exercise, by measuring the effects of 670 nm light on plasma nitrosothiols, leg perfusion, and gastrocnemius muscle health. If our hypotheses are correct, we will use results of this Phase II Trial to design a definitive clinical trial to test whether 670 nm light, a safe, accessible, and well-tolerated therapy, enhances the benefits of exercise, thereby improv...