title: Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial.
abstract: OBJECTIVE
  Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown.
  
  
  OBJECTIVE
  To investigate whether therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves exercise capacity in patients with intermittent claudication.
  
  
  METHODS
  In a phase 2 double-blind, placebo-controlled study, 159 patients (median [SD] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, Georgia, between January 2010 and July 2012.
  
  
  METHODS
  Participants were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 μg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily.
  
  
  METHODS
  The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating PC levels, ankle brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores.
  
  
  RESULTS
  Of the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% CI, 67 to 151]) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14 to 98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, -6 to 112], P = .08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7 to 16.1) vs 4.8 (95% CI, -0.1 to 9.6), with a mean difference in change for GM-CSF vs placebo of 7.5 (95% CI, 1.0 to 14.0; P = .03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4 to 18.7) vs 4.8 (95% CI, -0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2 to 15.7], P = .047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups.
  
  
  CONCLUSIONS
  Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up. The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01041417.
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Poole
authors.affiliation: Division of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
authors.forename: Kreton
authors.initials: K
authors.lastname: Mavromatis
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: José N
authors.initials: JN
authors.lastname: Binongo
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Ali
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Qunna
authors.initials: Q
authors.lastname: Li
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khayata
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rocco
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Topel
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
authors.forename: Charlene
authors.initials: C
authors.lastname: Brown
authors.affiliation: Division of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia6Division of Vascular and Endovascular Surgery, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Corriere
authors.affiliation: Georgia Regents University, University of Georgia, Augusta.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Murrow
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Salman
authors.initials: S
authors.lastname: Sher
authors.affiliation: Department of Radiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Clement
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Khuram
authors.initials: K
authors.lastname: Ashraf
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Amr
authors.initials: A
authors.lastname: Rashed
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Tarek
authors.initials: T
authors.lastname: Kabbany
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Robert
authors.initials: R
authors.lastname: Neuman
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Alanna
authors.initials: A
authors.lastname: Morris
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Arshad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Salim
authors.initials: S
authors.lastname: Hayek
authors.affiliation: Department of Radiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: John
authors.initials: J
authors.lastname: Oshinski
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Young-sup
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia7Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007279:Injections, Subcutaneous; D007383:Intermittent Claudication / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000628:therapy*; D013234:Stem Cells; D016896:Treatment Outcome; D016138:Walking
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor