A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia.

Abstract

BACKGROUND:

Critical limb ischemia portends a risk of major amputation of 25% to 35% within 1 year of diagnosis. Preclinical studies provide evidence that intramuscular injection of autologous CD34+ cells improves limb perfusion and reduces amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk critical limb ischemia, who were poor or noncandidates for surgical or percutaneous revascularization (ACT34-CLI).

METHODS AND RESULTS:

Twenty-eight critical limb ischemia subjects were randomized and treated: 7 to 1 × 10(5) (low-dose) and 9 to 1 × 10(6) (high-dose) autologous CD34+ cells/kg; and 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months postinjection, 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months, with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends toward improved amputation-free survival at 6 months and 12 months. No adverse safety signal was associated with cell administration.

CONCLUSIONS:

This study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later-phase clinical trials.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00616980.

• Authors: Douglas W Losordo, Melina R Kibbe, Farrell Mendelsohn, William Marston, Vickie R Driver, Melhem Sharafuddin, Victoria Teodorescu, Bret N Wiechmann, Charles Thompson, Larry Kraiss, Teresa Carman, Suhail Dohad, Paul Huang, Candice E Junge, Kenneth Story, Tara Weistroffer, Tina M Thorne, Meredith Millay, John Paul Runyon, Robert Schainfeld, Autologous CD34+ Cell Therapy for Critical Limb Ischemia Investigators
• Journal: Circulation. Cardiovascular interventions (Circ Cardiovasc Interv) Vol. 5 Issue 6 Pg. 821-30 (Dec 2012) ISSN: 1941-7632 [Electronic] United States
• PMID: 23192920 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, CD34
• Biomarkers

Topics

• Aged
• Aged, 80 and over
• Amputation, Surgical
• Analysis of Variance
• Antigens, CD34 (analysis)
• Biomarkers (analysis)
• Critical Illness
• Disease-Free Survival
• Double-Blind Method
• Female
• Humans
• Injections, Intramuscular
• Ischemia (physiopathology, surgery)
• Limb Salvage
• Lower Extremity (blood supply)
• Male
• Middle Aged
• Pilot Projects
• Prospective Studies
• Quality of Life
• Recovery of Function
• Stem Cell Transplantation (adverse effects)
• Stem Cells (immunology)
• Time Factors
• Transplantation, Autologous
• Treatment Outcome
• United States
• Wound Healing