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Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial.
JAMA. 2013 Dec 25; 310(24):2631-9.JAMA

Abstract

IMPORTANCE

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.

DESIGN, SETTING, AND PARTICIPANTS

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.

INTERVENTIONS

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.

MAIN OUTCOMES AND MEASURES

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 AND RELEVANCE

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.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01041417.

Authors+Show Affiliations

Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Division of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.Division of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.Division of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia6Division of Vascular and Endovascular Surgery, Emory University School of Medicine, Atlanta, Georgia.Georgia Regents University, University of Georgia, Augusta.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Department of Radiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.Department of Radiology, Emory University School of Medicine, Atlanta, Georgia.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.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.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24247554

Citation

Poole, Joseph, et al. "Effect of Progenitor Cell Mobilization With Granulocyte-macrophage Colony-stimulating Factor in Patients With Peripheral Artery Disease: a Randomized Clinical Trial." JAMA, vol. 310, no. 24, 2013, pp. 2631-9.
Poole J, Mavromatis K, Binongo JN, et al. Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial. JAMA. 2013;310(24):2631-9.
Poole, J., Mavromatis, K., Binongo, J. N., Khan, A., Li, Q., Khayata, M., Rocco, E., Topel, M., Zhang, X., Brown, C., Corriere, M. A., Murrow, J., Sher, S., Clement, S., Ashraf, K., Rashed, A., Kabbany, T., Neuman, R., Morris, A., ... Quyyumi, A. A. (2013). Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial. JAMA, 310(24), 2631-9. https://doi.org/10.1001/jama.2013.282540
Poole J, et al. Effect of Progenitor Cell Mobilization With Granulocyte-macrophage Colony-stimulating Factor in Patients With Peripheral Artery Disease: a Randomized Clinical Trial. JAMA. 2013 Dec 25;310(24):2631-9. PubMed PMID: 24247554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial. AU - Poole,Joseph, AU - Mavromatis,Kreton, AU - Binongo,José N, AU - Khan,Ali, AU - Li,Qunna, AU - Khayata,Mohamed, AU - Rocco,Elizabeth, AU - Topel,Matthew, AU - Zhang,Xin, AU - Brown,Charlene, AU - Corriere,Matthew A, AU - Murrow,Jonathan, AU - Sher,Salman, AU - Clement,Stephanie, AU - Ashraf,Khuram, AU - Rashed,Amr, AU - Kabbany,Tarek, AU - Neuman,Robert, AU - Morris,Alanna, AU - Ali,Arshad, AU - Hayek,Salim, AU - Oshinski,John, AU - Yoon,Young-sup, AU - Waller,Edmund K, AU - Quyyumi,Arshed A, PY - 2013/11/20/entrez PY - 2013/11/20/pubmed PY - 2014/1/1/medline SP - 2631 EP - 9 JF - JAMA JO - JAMA VL - 310 IS - 24 N2 - IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01041417. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/24247554/Effect_of_progenitor_cell_mobilization_with_granulocyte_macrophage_colony_stimulating_factor_in_patients_with_peripheral_artery_disease:_a_randomized_clinical_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2013.282540 DB - PRIME DP - Unbound Medicine ER -