Plasma-Lyte A and 25% Autologous PlasmaAutologous EPCsAutologous EPCs Transfected with human eNOS
Plasma-Lyte A and 25% Autologous Plasma: Single dose of 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Autologous EPCs: Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Autologous EPCs Transfected with human eNOS: Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Study summary
This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing eNOS, and the first to use combination gene and cell therapy for the treatment of cardiac disease.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
* Male or female 18-80 years of age
* Clinical diagnosis of anterior ST-elevation myocardial infarction within the last 30 days, with any one of the following 12-lead electrocardiographic changes:
* a) Greater than or equal to 1 mm ST elevation or new Q waves in 2 adjacent electrocardiographic precordial leads
* b) A new left bundle branch block AND and for patients presenting within 3 days of onset of chest pain an increase in cardiospecific enzymes (\>3x CK with, EITHER positive MB fraction or increase in troponin compared to institution laboratory normal ranges)
* Successful PCI with stent implantation to infarct-related artery within the last 30 days; defined as residual stenosis no greater than 30%, TIMI flow of at least 2 or greater and a reference diameter of at least \> 2mm
* Is considered hemodynamically stable at time of enrollment and immediately prior to cell delivery
* Screening LVEF must be no greater than 45% by echocardiography (determined by Simpson's method) performed at least 4 days after revascularization procedure. (All screening echos done within the first 4 days post-PCI must be repeated either by echocardiography or MRI prior to cell delivery to ensure that the variability does not exceed 10%)
* In the case of a previous myocardial infarction, documented LVEF must be 55% or greater
* Female participants MUST be surgically sterile, post-menopausal, have documented infertility, or are of child-bearing potential wih laboratory confirmation of non-pregnant state
* Provided written informed consent and is willing to comply with study follow-up visits
Exclusion Criteria:
* Significant unprotected left main disease (stenosis of 50% or greater on diagnostic angiography)
* An increase in LVEF by greater that 10% from initial LVEF evaluation for repeat assessments
* The presence of significant coronary lesions, other than the index lesion of the IRA
* A history of significant ventricular arrhythmia NOT related to index STEMI
* A history of cerebro-vascular accident or transient ischemic attack within 6 months of enrollment
* Meets at least one exclusion criterion for MRI (NB: Recent stent implantation is not an exclusion)
* Inability to undergo apheresis procedure (i.e.: poor venous access, laboratory abnormalities)
* A history of uncorrected significant valvular heart disease
* A history of left ventricular dysfunction prior to index STEMI
* A history of human immunodeficiency virus (HIV) or hepatitis B or C infection
* A history of malignancy within 5 years (Except for low-grade and fully resolved non-melanoma skin cancer)
* A history of allergy to gentamycin or amphotericin
* A history of Heparin-Induced Thrombocytopenia (HIT)
* A history of non-compliance
* Active inflammatory autoimmune disease requiring chronic immunosuppressive therapy
* Creatinine clearance \<60 by Cockcroft-Gault Calculator
* Confirmed pregnant or lactating
* Is enrolled in a current investigational drug or device trial
* Participant has received cell or gene therapy in past
* The presence of any significant co-morbidities that, in the investigator's opinion, would preclude the participant from taking part in the trial
* Inability to provide informed consent and comply with the follow-up visit schedule
Primary outcome measure(s)
Assessment of Global LVEF — Baseline to 6 months 1. A change in global left ventricular ejection fraction by cardiac MRI between those treated with cell/gene enriched EPCs versus placebo
2. Change in global left ventricular ejection fraction by cardiac MRI between those treated with non-transfected autologous EPCs versus eNOS transfected EPCs.
Trial sites (3)
Facility
City
Region
Status
University of Ottawa Heart Institute
Ottawa
Ontario
St. Michael's Hospital
Toronto
Ontario
L'institut de cardiologie de Montreal
Montreal
Quebec
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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