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Assess the safety and effectiveness of stem cell application with regard to improvement in regional myocardial function in patients receiving Trans-Myocardial Laser Revascularization (TMR) and stem cells.
Multiple case experiences and studies have been published reviewing clinical experiences with Carbon Dioxide Trans-Myocardial Laser Revascularization (TMR) and autologous bone marrow derived cell application. These experiences have demonstrated perfusion improvements, ejection fraction improvements and improvements in angina or heart failure symptoms. The investigators elected to examine the use of CD133 positive (CD133+) BM-derived stem cells because of their pluripotent nature and the fact that during the CD133 selection process inflammatory cells present in the bone marrow are being discarded. CD133+ is a recently discovered marker for more primitive bone marrow derived multipotent stem and endothelial progenitor cells and is of particular interest in studies directed to therapeutic angiogenesis, as these cells have been shown to differentiate into endothelial and myogenic cell lines. Multiple studies have utilized BM derived cells for myocardial regeneration. Patients who received CD133+ cells showed improved perfusion at injection sites of stem cells leading to a significant increase in volume of left ventricular ejection fraction, regional wall motion in the infarct zone, and a reduction in end systolic left ventricular volume.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase I Open Label | Experimental | open label bone marrow derived autologous CD133+ selected stem cell application in patients receiving trans-myocardial laser revascularization to improve regional myocardial function as detailed below: Drug: CD133+ selected stem cells Dosage: Single injection of 0.1-0.2 ml around each laser channel Frequency: 10-20 channels Duration: Trans-Myocardial Revascularization |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bone Marrow Derived Autologous CD133+ Selected Cell Product | Drug | Injection of bone marrow derived autologous CD133+ cell product into laser channels during Trans-Myocardial Revascularization |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Treatment-emergent serious adverse events (SAE) and adverse events | Major adverse cardiac event and adverse events defined in the common toxicity criteria | Assess from Procedure through 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in left ventricular ejection fraction compared to baseline | Measured as a percentage by Echocardiography | Assessed at baseline, 6 months, and 12 months |
| Change in myocardial regional function compared to baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Sekela, MD | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky Healthcare | Lexington | Kentucky | 40536 | United States |
to be determined per principal investigator and statistician
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|
Measured by nuclear scanning.
| Assessed at baseline and 6 months |
| Change in myocardial regional viability compared to baseline | Measured by nuclear scanning. | Assessed at baseline and 6 months |
| Change in distance walked compared to baseline | Measured in feet during a 6 minute walk test | Assessed at baseline, 3 months, 6 months, and 12 months |
| Change in quality of life associated with heart failure compared to baseline | Measured using the Kansas City Cardiomyopathy Questionnaire. | Assessed at baseline, 3 months, 6 months, and 12 months |
| Change in class of angina compared to baseline | Measured using the Canadian Cardiovascular Society Grading Scale. | Assessed at baseline, 3 months, 6 months, and 12 months. |
| Change in class of heart failure compared to baseline | Measured using the New York Heart Association Questionnaire | Assessed at baseline, 3 months, 6 months, and 12 months. |
| Change in regional left ventricular wall motion compared to baseline | Measured using echocardiogram. | Assessed at baseline, 6 months, and 12 months |
| Change in quality of life associated with angina compared to baseline | Measured using the Seattle Angina Questionnaire | Assessed at baseline, 3 months, 6 months, and 12 months |