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.

Abstract

BACKGROUND:

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.

METHODS AND RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Niels van Royen, Stephan H Schirmer, Bektas Atasever, Casper Y H Behrens, Dirk Ubbink, Eva E Buschmann, Michiel Voskuil, Pieter Bot, Imo Hoefer, Reinier O Schlingemann, Bart J Biemond, J G Tijssen, Christoph Bode, Wolfgang Schaper, Jacques Oskam, Dink A Legemate, Jan J Piek, Ivo Buschmann
• Journal: Circulation (Circulation) Vol. 112 Issue 7 Pg. 1040-6 (Aug 16 2005) ISSN: 1524-4539 [Electronic] United States
• PMID: 16087795 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Recombinant Proteins
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Angioplasty, Balloon
• Arterial Occlusive Diseases (drug therapy, surgery, therapy)
• Arteries (drug effects)
• Blood Flow Velocity (drug effects)
• Brachial Artery (drug effects, pathology)
• Coronary Artery Bypass
• Exercise Test
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, therapeutic use)
• Humans
• Injections, Subcutaneous
• Pilot Projects
• Placebos
• Recombinant Proteins
• Skin (blood supply)
• Walking (physiology)