Mesenchymal Stem Cells and Myocardial Ischemia

Study Overview
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Brief Summary
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Ischemic cardiomyopathies are a leading cause of death in both men and women. When a person has a heart attack, blood is unable to reach a certain area of the heart, and if the blood supply is not re-established quickly, that area of the heart can suffer permanent damage. While recovery from a heart attack can be managed through medications and lifestyle changes, these treatments can not reverse the all damage to the heart. Current research is focusing on the development of cell-based therapies using stem cells to repair organs that have been irreversibly damaged by disease. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair. This study will evaluate the safety of injecting MSCs directly into the heart to repair and restore heart function in people who have had a heart attack and who have chronic myocardial ischemia with heart failure.

Detailed Description
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Mesenchymal stem cells from the bone marrow can differentiate into endothelial cells and participate in the development of new blood vessels in ischemic tissue. The aim of the study is in a phase I safety study to evaluate the clinical effect of autologous mesenchymal stem cell therapy in patients with severe chronic myocardial ischemia.10 patients with reversible ischemia on a SPECT will be treated with direct intramyocardial injections of autologous isolated and expanded mesenchymal stem cells.Clinical and objective evaluations will be performed at baseline and during 24 months follow-up.

Official Title
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Administration of Mesenchymal Stem Cells in Patients With Chronic Ischemic Cardiomyopathy

Conditions
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Chronic Myocardial Ischemia, Left Ventricular Dysfunction

Intervention / Treatment
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* Genetic: Mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 75 Male or female NYHA (Heart failure) Class II-IV or Angina pectoris CCS Class III or IV or symptoms consistent with) Chronic coronary artery disease with left ventricular function below 35% Stable medical therapy for at least one month Reversible perfusion defects by SPECT Not a candidate for coronary artery by-pass surgery due to poor targets or small vessels and not a candidate for percutaneous intervention due to small vessels or unreachable coronary lesions due to complicated anatomy Implantable Cardiovertor Defibrillator Exclusion Criteria: Acute coronary syndrome, revascularization (PCI or CABG), or cardiac resynchronization during the last 3 months Sustained ventricular Further revascularization planned for the next 30 days. Chronic atrial fibrillation. A wall thickness in the target region <8 mm as determined by 2D echocardiography (the target region is defined at the time of NOGA® mapping). An LV thrombus. Severe peripheral vascular disease precluding femoral artery access as determined at time of original catheterization. Aortic stenosis as determined as valve area less than 1 cm2 that prohibits catheter access to the LV. Human immunodeficiency virus (HIV1-2), HTLV-1 and 2. An active uncontrolled infection. A prosthetic aortic valve. A current or prior history within the last 3 years of neoplasm (excluding basal cell) and/or any active neoplasm within the last 24 months. Pregnancy or breastfeeding. Active participation in other research therapy for cardiovascular repair/regeneration. Any medical condition that would affect the investigator's ability to evaluate the subject's condition or could compromise the subject's safety. Any condition that, in the judgment of the investigator, would prohibit the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br> | Genetic: Mesenchymal stem cells<br>* 60x106 MSCs Trans-endocardial intramyocardial injections (n=14-16)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and feasibility of transendocardial injection using the NogaStar XP Mapping Catheter with the MyostarTM Left Ventricular Injection Catheter of autologous MSC in subjects with chronic myocardial ischemia and left ventricular dysfunction |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in SF-36, VO2max, 6 min walk test, and the NYHA, CCS Classifications Effect related to cardiac function |  | 30 days to 2 years |