Rationale and design of Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT-AMI): the first randomized placebo-controlled trial of enhanced progenitor cell therapy for acute myocardial infarction.
BACKGROUND
Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction (MI) patients is often modest or even absent. Unlike classical pharmacological treatments, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. However, a major limitation of autologous cell therapy is the deleterious influence of age and cardiac risk factors on progenitor cell activity.


METHODS
The ENACT-AMI trial is a phase IIb, double-blind, randomized placebo-controlled trial, using transplantation of autologous early endothelial progenitor cells (EPCs) for patients who have suffered large MI. Circulating mononuclear cells (MNCs) are obtained by apheresis and subjected to differential culture for 3 days to select a population of highly regenerative, endothelial-like, culture modified MNCs (E-CMMs), often referred to as "early EPCs." A total of 99 patients will be randomized to placebo (Plasma-Lyte A), autologous E-CMMs, or E-CMMs transfected with human endothelial nitric oxide synthase delivered by coronary injection into the infarct-related artery. The primary efficacy end point is change from baseline to 6 months in global left ventricular ejection fraction by cardiac MRI; secondary endpoints include regional wall motion, wall thickening, infarct volume, time to clinical worsening, and quality of life.


CONCLUSIONS
This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing endothelial nitric oxide synthase, and the first to use combination gene and cell therapy for the treatment of cardiac disease.
Taljaard
Monica
M
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada. mtaljaard@ohri.ca
Ward
Michael R
MR
Kutryk
Michael J B
MJ
Courtman
David W
DW
Camack
Nancy J
NJ
Goodman
Shaun G
SG
Parker
Thomas G
TG
Dick
Alexander J
AJ
Galipeau
Jacques
J
Stewart
Duncan J
DJ
D004311:Double-Blind Method; D006801:Humans; D009203:Myocardial Infarction / Q000601:surgery*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D012107:Research Design; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000201:enzymology*; D014162:Transfection; D014182:Transplantation, Autologous; D015854:Up-Regulation
D052250:Nitric Oxide Synthase Type III