START Trial: a pilot study on STimulation of ARTeriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-08, Vol.112 (7), p.1040-1046
• Main Authors: van Royen, Niels, Schirmer, Stephan H, Atasever, Bektas, Behrens, Casper Y H, Ubbink, Dirk, Buschmann, Eva E, Voskuil, Michiel, Bot, Pieter, Hoefer, Imo, Schlingemann, Reinier O, Biemond, Bart J, Tijssen, J G, Bode, Christoph, Schaper, Wolfgang, Oskam, Jacques, Legemate, Dink A, Piek, Jan J, Buschmann, Ivo
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon; Arterial Occlusive Diseases - drug therapy; Arterial Occlusive Diseases - surgery; Arterial Occlusive Diseases - therapy; Arteries - drug effects; Blood Flow Velocity - drug effects; Brachial Artery - drug effects; Brachial Artery - pathology; Coronary Artery Bypass; Exercise Test; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Humans; Injections, Subcutaneous; Pilot Projects; Placebos; Recombinant Proteins; Skin - blood supply; Walking - physiology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.104.529552

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently shown to increase collateral flow index in patients with coronary artery disease. Experimental models showed beneficial effects of GM-CSF on collateral artery growth in the peripheral circulation. Thus, in the present study, we evaluated the effects of GM-CSF in patients with peripheral artery disease. A double-blinded, randomized, placebo-controlled study was performed in 40 patients with moderate or severe intermittent claudication. Patients were treated with placebo or subcutaneously applied GM-CSF (10 microg/kg) for a period of 14 days (total of 7 injections). GM-CSF treatment led to a strong increase in total white blood cell count and C-reactive protein. Monocyte fraction initially increased but thereafter decreased significantly as compared with baseline. Both the placebo group and the treatment group showed a significant increase in walking distance at day 14 (placebo: 127+/-67 versus 184+/-87 meters, P=0.03, GM-CSF: 126+/-66 versus 189+/-141 meters, P=0.04) and at day 90. Change in walking time, the primary end point of the study, was not different between groups. No change in ankle-brachial index was found on GM-CSF treatment at day 14 or at day 90. Laser Doppler flowmetry measurements showed a significant decrease in microcirculatory flow reserve in the control group (P=0.03) and no change in the GM-CSF group. The present study does not support the use of GM-CSF for treatment of patients with moderate or severe intermittent claudication. Issues that need to be addressed are dosing, the selection of patients, and potential differences between GM-CSF effects in the coronary and the peripheral circulation.