title: 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.
  
  
  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.affiliation: Department of Cardiology, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. n.vanroyen@amc.uva.nl
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Schirmer
authors.forename: Bektas
authors.initials: B
authors.lastname: Atasever
authors.forename: Casper Y H
authors.initials: CY
authors.lastname: Behrens
authors.forename: Dirk
authors.initials: D
authors.lastname: Ubbink
authors.forename: Eva E
authors.initials: EE
authors.lastname: Buschmann
authors.forename: Michiel
authors.initials: M
authors.lastname: Voskuil
authors.forename: Pieter
authors.initials: P
authors.lastname: Bot
authors.forename: Imo
authors.initials: I
authors.lastname: Hoefer
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
authors.forename: J G
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
authors.forename: Jacques
authors.initials: J
authors.lastname: Oskam
authors.forename: Dink A
authors.initials: DA
authors.lastname: Legemate
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Ivo
authors.initials: I
authors.lastname: Buschmann
mesh_terms: D000800:Angioplasty, Balloon; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000601:surgery / Q000628:therapy; D001158:Arteries / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000473:pathology; D001026:Coronary Artery Bypass; D005080:Exercise Test; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D010865:Pilot Projects; D010919:Placebos; D011994:Recombinant Proteins; D012867:Skin / Q000098:blood supply; D016138:Walking / Q000502:physiology
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor