Design of the START-trial: STimulation of ARTeriogenesis using subcutaneous application of GM-CSF as a new treatment for peripheral vascular disease. A randomized, double-blind, placebo-controlled trial.

Abstract

Peripheral arterial disease (PAD) affects a large percentage of the elderly population. Standard invasive treatment, apart from risk factor modulation, consists of bypass surgery or percutaneous transluminal angioplasty. However, symptomatic recurrence rates are high for both procedures and a substantial part of the patient population with PAD is not a candidate for invasive revascularization due to complexity of the lesion and/or co-morbidity. Therapeutic arteriogenesis has been proposed as an alternative treatment option. The present paper describes the design of the START-trial. This trial aims to determine the potential of the pro-arteriogenic substance granulocyte/macrophage colony stimulating factor (GM-CSF) to increase maximal walking distance in patients with intermittent claudication. A double-blinded, randomized, placebo-controlled study will be performed in 40 patients with peripheral obstructive arterial disease Rutherford grade I, category 2 or 3, that are candidates for bypass surgery or percutaneous transluminal angioplasty. Based on pharmacokinetic and toxicologic studies, a dose of 10 microg/kg will be used. Patients will be treated for a period of 14 days on each consecutive day, with the last injection applied on day 12. The primary endpoint will be the change in walking distance from day 0 to day 14 as assessed by an exercise treadmill test. Secondary endpoints will be the ankle-brachial index at rest and after exercise, the pain-free walking distance and cutaneous microcirculatory alterations as assessed by laser Doppler fluxmetry. Iliac flow reserve and conductance will be measured by magnetic resonance imaging.

• Authors: Niels van Royen, Jan J Piek, Dink A Legemate, Wolfgang Schaper, Jacques Oskam, Bektas Atasever, Michiel Voskuil, Dirk Ubbink, Stephan H Schirmer, Ivo Buschmann, Christoph Bode, Eva E Buschmann
• Journal: Vascular medicine (London, England) (Vasc Med) Vol. 8 Issue 3 Pg. 191-6 ( 2003) ISSN: 1358-863X [Print] England
• PMID: 14989560 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Arterial Occlusive Diseases (drug therapy, physiopathology)
• Arteries (drug effects, growth & development)
• Blood Flow Velocity (drug effects)
• Collateral Circulation (drug effects)
• Double-Blind Method
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, pharmacology, therapeutic use)
• Humans
• Injections, Subcutaneous
• Intermittent Claudication (drug therapy, physiopathology)
• Neovascularization, Physiologic (drug effects)
• Research Design