In a clinical trial of 210 participants with peripheral artery disease (PAD), granulocyte-macrophage colony-stimulating factor (GM-CSF) did not improve walking ability, although exercise did lead to significant improvements, according to Northwestern Medicine researchers.
GM-CSF was designed to increase circulating stem cells in the blood. Colony-stimulating factors mobilize progenitor cells from bone marrow and spleen into the peripheral circulation and it was thought they would improve walking performance in people with PAD by promoting angiogenesis and improving endothelial function and cardiovascular health.
The study, published yesterday in the Journal of the American Medical Association (JAMA), was led by Mary McDermott, the Jeremiah Stamler Professor of Medicine at Northwestern University Feinberg School of Medicine.
"There is a lot of interest in stem cell therapy, and this is the largest trial of this type of therapy conducted to date in people with blockages in their leg arteries," McDermott said. "It was disappointing that we did not see a benefit from this because so few therapies are available for patients with peripheral artery disease, and earlier research suggested this drug may be beneficial. More research is needed to identify new effective therapies."
The team randomized 210 participants with PAD to one of four groups: GM-CSF with exercise, GM-CSF alone, exercise alone (with placebo) or a control that received no active therapies. The exercise consisted of supervised treadmill exercises completed three times weekly for six months. The GM-CSF and the placebo were administered via injection three times a week for the first two weeks of the intervention.
The trial showed that at 12 weeks after the intervention, the drug therapy had not led to improved walking performance, either alone or combined with exercise. Still, the data showed that exercise significantly improved patients' six-minute walking distance, as compared to the control.
"Although this trial showed no added benefit of stem cell mobilization by GM-CSF in individuals with PAD, it yet again confirmed the benefits of exercise on walking capacity that have been observed in previous studies," said Dr. Diane Reid, a National Heart, Lung and Blood Institute (NHLBI) project officer for the study and a medical officer in the NHLBI Vascular Biology and Hypertension Branch. "Prompt reporting of negative clinical trial results, as done here, provides valuable information to guide the future directions of research on potential new therapeutics."