Far Red Light to Improve Functioning in PAD: the LIGHT PAD Trial

Project: Research project

Project Details


Lower extremity peripheral artery disease (PAD) affects 10-15% of people age 65 and older and 15 to 20% of those age 75 and older. Older people with PAD have greater functional impairment, faster functional decline, and higher rates of mobility loss than people without PAD. In PAD, reduced perfusion of gastrocnemius muscle is associated with increased gastrocnemius oxidative stress, mitochondrial impairment, and muscle fiber damage. Yet few non-invasive therapies improve functioning in people with PAD. Nitric oxide (NO) is a signaling molecule with therapeutic properties that improve perfusion and reverse the skeletal muscle pathology in PAD. In preclinical studies, NO increases angiogenesis and perfusion, protects against ischemic injury, enhances skeletal muscle mitochondrial activity, and activates satellite cells, which restore and repair skeletal muscle. Interventions that increase NO bioavailability have major therapeutic potential for people with PAD. Nitrosothiols are a major source of NO and NO bioactivity. Preclinical studies and our preliminary human evidence show that far red light (at wavelength of 670 nm) releases nitrosothiols, nitrite, and other vasoactive species. Four pilot studies completed in preparation for this proposal showed that a single dose of far red light therapy increased plasma nitrosothiols, improved lower extremity blood flow, and meaningfully improved functional performance in people with PAD. Therefore, we propose a Phase II randomized clinical trial to collect preliminary data to test whether four months of daily far red light treatment of the lower extremities improves walking performance, lower extremity perfusion, and ischemia-related gastrocnemius muscle damage in people with PAD, compared to a sham control. Thirty- two people with PAD will be randomized to 10 minutes of daily home treatment with either far red light or a sham light for four months. Our primary outcome is change in six-minute walk distance at 4-month follow-up. In secondary and exploratory aims, we will distinguish between acute and chronic effects of far red light on six-minute walk, measure the effects of far red light on treadmill walking performance and patient-reported outcomes, and delineate biologic pathways by which far red light improves walking performance in PAD, by measuring change in plasma nitrite and nitrosothiols, gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health and mitochondrial activity (measured by muscle biopsy). If our hypotheses are supported by this Phase II trial, results will be used to design a definitive randomized trial of far red light for people with PAD. If far red light improves functional performance in PAD, this simple, accessible, and well tolerated therapy will have a major impact on preventing mobility loss and improving quality of life in the large and growing number of older people disabled by PAD.
Effective start/end date2/1/231/31/25


  • National Institute on Aging (5R21AG080426-02)


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