The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction Trial (ENACT-AMI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Ottawa Hospital Research Institute
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00936819
First received: July 7, 2009
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Anterior Wall Myocardial Infarction
Biological: Plasma-Lyte A and 25% Autologous Plasma
Biological: Autologous EPCs
Biological: Autologous EPCs Transfected with human eNOS
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb, Randomized, Double-blind, Placebo Controlled Study Using Transplantation of Autologous Early Endothelial Progenitor Cells(EPCs) for Patients Who Have Suffered Acute Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Assessment of Global LVEF [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Assessment of: Cardiac wall motion and volumes [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    1. Change in regional wall motion and regional wall thickening by cardiac MRI between the above patient groups
    2. Change in echocardiographic assessment of LVEF, infarct size and ventricular volumes between the above patient groups

  • Time To Clinical Worsening (TTCW) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    Quality of Life Measures: Participants will complete SF-36 and DASI questionnaires at baseline, 3 and 6 months.

  • Safety Measurements [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: Yes ]
    1. Clinically significant changes in CK and troponin more than 24 hours post delivery
    2. Clinically significant changes in ECG
    3. Assessment of major acute cardiac events
    4. Evidence of any systemic embolization during the hospitalization period
    5. Need for revacularization procedures


Estimated Enrollment: 100
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Plasma-Lyte A and 25% autologous plasma Biological: Plasma-Lyte A and 25% Autologous Plasma
Single dose of 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Experimental: Autologous EPCs Biological: Autologous EPCs
Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Other Name: Non-applicable
Experimental: Autologous EPCs Transfected with human eNOS Biological: 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
Other Name: Non-applicable

Detailed Description:

Introduction:

  • Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction patients is often modest or in some cases absent. Unlike classical re-perfusion therapies, which must be delivered before irreversible cardiac damage has occurred, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. A number of clinical trials have been performed, mainly using autologous bone marrow cells, and these suggest a significant albeit modest improvement in cardiac function post MI. However, a major limitation of autologous cell therapy in patients with cardiovascular disease is the deleterious influence of age and other cardiac risk factors on progenitor cell activity, which may limit greatly the potential efficacy of this promising approach.

Trial Design:

  • The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction (ENACT-AMI) trial is a Canadian, 5-center, phase IIb, double-blind, parallel, randomized placebo controlled trial assessing the safety and efficacy of cell and gene therapy for patients with moderate to large anterior STEMI and who have undergone re-vascularization with stent implantation to the infarct related artery (IRA). The anticipated recruitment target is 100 patients over a two-year period.
  • Consenting participants who qualify during the screening process, will undergo apheresis. Randomization, through a web-based system will take place immediately after successful apheresis. The cell collection samples will be sent to a cell manufacturing facility for manufacturing according to the treatment allocation of: a)Placebo (Plasma-Lyte A & 25% autologous plasma), b)EPCs or c)EPCs transfected with human endothelial nitric oxide synthase (eNOS).
  • Approximately 5-7 days later, the patient will receive the randomized treatment allocation via intracoronary injection into the IRA. Participants will remain in hospital overnight for continuous cardiac monitoring. The first post-delivery visit will take place the following morning before hospital discharge. Subsequent study visits will be clinic visits at 1 week, 1, 3 and 6 months after study treatment. Subsequently, a registry to collect long-term safety information from telephone contacts will continue annually for 10 years. During the registry period, participants will be allowed to volunteer for enrolment in other clinical trials.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 2 mm ST elevation) in 2 adjacent electrocardiographic precordial leads
  • b) A new left bundle branch block AND and an increase in cardiospecific enzymes (>3x CK, and 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 and a reference diameter of at least > 2mm
  • Is considered hemodynamically stable at time of enrollment and immediately prior to cell delivery
  • Screening LVEF for the first 12 enrolled participants, must be no greater than 40% by echocardiography (determined by Simpson's method) performed at least 2 days after revascularization procedure. Subsequent participants enrolled in the trial, must have an LVEF no greater than 45%. (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 50% 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936819

Contacts
Contact: Dr. Duncan J. Stewart, MD FRCP C (613) 737-8899 ext 79017 djstewart@ohri.ca
Contact: Leslie Carlin, RN (613) 798-5555 ext 13633 lcarlin@ohri.ca

Locations
Canada, Ontario
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Christopher Glover, MD FRCP C    (613) 761-4119    cglover@ottawaheart.ca   
Contact: Leslie Carlin, RN    (613) 798-5555 ext 13633    lcarlin@ohri.ca   
Principal Investigator: Christopher Glover, MD FRCP C         
Sub-Investigator: Alexander Dick, MDCRP C         
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Michael Kutryk, MDFRCP C    416-864-6060 ext 6155    kutrykm@smh.toronto.on.ca   
Contact: TBD         
Principal Investigator: Michael Kutryk, MD         
Sunnybrook Hospital Not yet recruiting
Toronto, Ontario, Canada, M4N3M5
Contact: Bradley Strauss, MD FRCP C    416-480-6066    bradley.strauss@sunnybrook.ca   
Contact: TBD         
Principal Investigator: Bradley Strauss, MD         
Canada, Quebec
Jewish General Hospital Not yet recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Dominique Joyal, MD FRCP C    514-340-8222    djoyal@mcgill.ca   
Contact: TBD         
Principal Investigator: Dominique Joyal, MD FRCP C         
L'insitut de cardiologie de Montreal Not yet recruiting
Montreal, Quebec, Canada, H1T 1C8
Contact: Quoc Hung.Ly, MD FRCP C    514-376-3330 ext 2438    hung.ly@icm.mhi.org   
Contact: TBD         
Principal Investigator: Quoc Hung-Ly, MDFRCP C         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Duncan Stewart, MD, FRCP C Ottawa Hospital Research Institute
  More Information

No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00936819     History of Changes
Other Study ID Numbers: 2008-872, ISRCTN47943321
Study First Received: July 7, 2009
Last Updated: May 12, 2014
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
Stent
endothelial progenitor cells
nitric oxide
myocardial infarction
MRI

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Anterior Wall Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Plasma-lyte 148
Ophthalmic Solutions
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014