TELmisartan plus EXercise to improve functioning in PAD: The TELEX Trial

In people with lower extremity peripheral artery disease (PAD), ischemia-reperfusion of calf skeletal muscle during walking is associated with calf muscle fiber atrophy and impaired calf muscle mitochondria function. These calf muscle abnormalities are associated with functional impairment and mobility loss in people with PAD. Yet few medical therapies exist to improve mobility or prevent disability in PAD patients. Recent evidence suggests that the angiotensin receptor blocker (ARB) telmisartan may ameliorate the skeletal muscle dysfunction present in PAD. In normal mice, telmisartan increases Type I skeletal muscle fibers, improves mitochondrial function, increases oxygen consumption, and enhances exercise performance. Also in mice, ARBs reduce fibrosis after muscle injury and enhance satellite cell-dependent muscle regeneration after muscle injury. We hypothesize that these favorable effects of ARBs and telmisartan on skeletal muscle in mice may benefit the ischemia-reperfusion related calf muscle injury observed in patients with PAD. In support of our hypothesis, a small trial in humans showed that telmisartan improved treadmill walking performance in people with PAD. The primary aims of the TELEX Study are to a) definitively establish whether telmisartan alone improves walking performance in people with PAD compared to placebo and b) determine whether the combination of telmisartan plus supervised exercise improves walking performance more than telmisartan alone and supervised exercise alone, respectively. To achieve our aims, we will conduct a randomized controlled clinical trial (2 x 2 factorial design) of 220 PAD participants randomized to one of four arms: Group A: telmisartan + supervised exercise therapy; Group B: telmisartan + a “no exercise” control group; Group C: placebo + supervised exercise therapy; and Group D: placebo + a “no exercise” control group. Our primary outcome is change in six-minute walk performance between bas