Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions
This phase I clinical trial will evaluate the safety and efficacy of intra-coronary injection of AC133 selected autologous marrow-derived stem cells in patients with chronic coronary artery occlusion. A clinical study to determine the therapeutic potential of marrow-derived stem cells as an adjunct therapy to current standard therapies for CAD is warranted. The current initiative is to investigate a model of chronic myocardial ischemia and (1) to determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans and (2) if this treatment shows any improvement in coronary perfusion, as assessed using non-invasive imaging. This study is structured to evaluate the feasibility and safety of autologous AC133+ bone marrow-derived stem cell via intra-coronary injection into documented ischemic but viable myocardial zones via established collateral vessels. The epicardial vessel that normally supplies the ischemic zone must be 100% chronically occluded and considered non-revascularizable by percutaneous means.
Procedure: catheter-based intracoronary injection
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions|
- Assess the safety and feasibility of performing autologous AC133+ selected bone marrow-derived stem cell intra-coronary infusion and determine whether any benefit is achieved from the infusion of stem cells by non-invasive cardiac assessment.
- Improvement in ETT, reduction in ischemic area, viability improvement (nuclear stress imaging), improvement in angina (Seattle Angina Questionnaire), major adverse cardiac events assessment, echocardiogram assessment of left %EF and regional wall motion.
|Study Start Date:||January 2006|
|Study Completion Date:||June 2008|
|Primary Completion Date:||June 2007 (Final data collection date for primary outcome measure)|
This study is composed of one phase. The objective of Phase I is to assess the safety and feasibility of performing escalating doses of autologous AC133+ selected bone marrow-derived stem cell with intracoronary infusion via epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of a chronic totally occluded vessel. Additionally, focus on the assessment of the benefit achieved from the infusion of stem cells and subsequent angiogenesis at 6 months will be observed.
Potential candidates are patients with a known total occlusion of an epicardial vessel, with a documented chronically ischemic territory supplied by collateral conduits.
Secondary Objectives include:
- Improvement in ETT as determined by: total exercise duration on the 6 month ETT in seconds time to: onset of angina, one mm ST depression, onset of angina or one mm ST depression (whichever occurs first)
- Reduction in the area of ischemia will be evaluated by nuclear (sestamibi) stress imaging with exercise or pharmacologic stress.
- Improvement in viability within the chronically ischemic zone as measured by nuclear (sestamibi) stress imaging.
- Improvement in angina as per Angina Questionnaire (The Seattle Angina Questionnaire) at 7, 14, 30, 90, 180, and 365 days.
Major adverse cardiac events (MACE) assessment (composite endpoint including cardiac death, myocardial infarction, ischemia-driven target vessel revascularization, CABG, CVA, and rehospitalization for angina), MACE definitions:
Myocardial Infarction (All ST segment elevation MIs as diagnosed on electrocardiogram by a staff cardiologist and all non-ST segment elevation MIs as defined by elevation in cardiac enzyme markers per the hospital laboratory guidelines) Cerebral Vascular Accidents (e.g., acute neurological event).
- Concomitant Medication usage (e.g., changes in utilization of PRN or sublingual nitroglycerin for angina)
- ECG changes at day of discharge, 7, 14, 30, 90, 180, and 365 days.
- Functional capacity (e.g., exercise duration (time) and changes in METS achieved on treadmill study at 6 month follow-up).
- Echocardiogram assessment of left ventricular ejection fraction and regional wall motion abnormalities at 180 days (e.g., changes in regional wall motion score and/or changes in left ventricular ejection fraction).
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Principal Investigator:||Dale Adler, MD||Case Western Reserve University|
|Principal Investigator:||Hillard Lazarus, MD||Case Western Reserve University|