Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
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:
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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)
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Reduction in the area of ischemia will be evaluated by nuclear (sestamibi) stress imaging with exercise or pharmacologic stress.
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Improvement in viability within the chronically ischemic zone as measured by nuclear (sestamibi) stress imaging.
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Improvement in angina as per Angina Questionnaire (The Seattle Angina Questionnaire) at 7, 14, 30, 90, 180, and 365 days.
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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).
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Concomitant Medication usage (e.g., changes in utilization of PRN or sublingual nitroglycerin for angina)
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ECG changes at day of discharge, 7, 14, 30, 90, 180, and 365 days.
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Functional capacity (e.g., exercise duration (time) and changes in METS achieved on treadmill study at 6 month follow-up).
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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).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Treatment with autologous bone marrow (BM)-derived CD133+ stem cell therapy The Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. |
Biological: Catheter-based intracoronary injection
This Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Nine patients were received CD133+ cells into epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of the CTO.
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Outcome Measures
Primary Outcome Measures
- 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. [7days-6months]
Determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans
Secondary Outcome Measures
- 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. [7 days-6months]
Determine if this treatment shows any improvement in coronary perfusion, as assessed using non-invasive imaging.
Eligibility Criteria
Criteria
Inclusion Criteria:
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The patient must have at least one region of chronically ischemic myocardium formerly perfused by a coronary artery which is now 100% occluded and not revascularizable by conventional percutaneous or surgical methods.
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Well-established collateral vessels at least 1.5-mm luminal diameter by coronary angiography to the chronically ischemic myocardium must be identified at the time of diagnostic coronary angiography.
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Evidence of viable myocardium in the area supplied by collateral conduits intended for stem cell infusion must be demonstrated by nuclear (sestamibi) stress imaging.
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Left ventricular ejection fraction of >45% as per 2D echocardiogram.
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Patient must experience class II - IV angina as defined by the Canadian Cardiovascular Society (CCS).
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Patient will be followed by the investigating team over the 12 month follow-up period.
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The patient must be at least 18 years of age and have signed an informed consent.
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If the patient is a female of child-bearing potential, a pregnancy test is negative.
Exclusion Criteria:
Patients meeting any of the following exclusion criteria will be excluded from the study:
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Patient with coronary lesions amenable to percutaneous coronary intervention including brachytherapy, or where CABG is indicated.
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Any contraindication for cardiac catheterization and percutaneous coronary intervention as per institutional guidelines.
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Any contraindication for bone marrow aspiration as per institutional guidelines.
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Myocardial infarction within the previous 3 months.
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Documented bleeding diathesis.
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Known malignancy involving the hematopoietic/lymphoid system.
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Patients with baseline ECG abnormalities that would hinder interpretation of baseline ECG uninterpretable for ischemia (e.g., left bundle branch block, left ventricular hypertrophy with strain pattern, Wolff-Parkinson-White syndrome).
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Patients with severe co-morbidities including renal failure (serum creatinine > 2.0).
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Anticipated unavailability for follow-up visits secondary to psychological or social reasons.
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NYHA class III or IV congestive heart failure
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Anemia with hemoglobin concentration < 8 mg/dl
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Thrombocytopenia with platelet count < 100 x 103
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Case Western Reserve University | Cleveland | Ohio | United States | 44106 |
Sponsors and Collaborators
- Case Western Reserve University
- University Hospitals Cleveland Medical Center
- Arteriocyte, Inc.
Investigators
- Principal Investigator: Dale Adler, MD, Case Western Reserve University
- Principal Investigator: Hillard Lazarus, MD, Case Western Reserve University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HFM-705