Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease

Atherosclerotic peripheral artery disease (PAD) of the lower extremities afflicts up to 8% of the U.S. population and lack of adequate sustainable therapies necessarily results in severe morbidity and increased mortality. Both experimental and current clinical data indicate that GM-CSF has the capacity to mobilize a variety of progenitor cells (PCs), including endothelial PCs that appear to improve ischemia. This study builds on the findings of prior research which showed improvements in claudication symptoms after treatment with GM-CSF. This study aims to answer whether repeat administration of GM-CSF at 3 months will further improve symptoms. The researchers will investigate in a double-blind placebo-controlled randomized study whether 3 weeks of three-times-a-week injection of GM-CSF will improve measures of ischemia in patients with intermittent claudication. This study will recruit 176 participants with atherosclerotic PAD and claudication. After screening for inclusion and exclusion criteria, eligible subjects will be trained to perform subcutaneous injections and instructed to walk until they develop claudication or symptomatic limitation at least three times a day for 4 weeks. At the end of the 4-week period, subjects will undergo baseline testing and will be randomized to receive 500 μg/day of GM-CSF thrice weekly for 3 weeks (group A) or a placebo (group B). After 3 months, follow-up endpoint testing will be performed. Subjects in group A will then receive the second administration of 500 μg/day of subcutaneous GM-CSF thrice weekly for another 3 weeks and be followed for another 3 months for endpoint measurements, while Group B subjects will receive a matching placebo. The primary outcome is change in walking performance in the active treatment group after 6 months compared to the placebo group. The secondary outcome includes change in peak walking time at 6 months, changes in circulating progenitor cell levels, ankle brachial index (ABI), walking impairment questionnaire (WIQ) scores, and 36-item Short-Form Health Survey (SF-36) scores. Long-term follow up, by way of a telephone call, will occur with each participant one, two and three years after they enrolled in the study to administer questionnaires and collect adverse event data. In response to the Coronavirus Disease 2019 (COVID-19) crisis on April 3, 2020 the Institutional Review Board (IRB) approved temporary modifications to this study to postpone study visits that do not involve active drug/placebo use.