Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy

Study Overview
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Brief Summary
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Several studies have documented that transplantation of bone marrow-derived cells (BMC) following acute myocardial infarction is associated with a reduction in infarct scar size and improvements in left ventricular function and perfusion. The available evidence in humans suggests that BMC transplantation is associated with improvements in physiologic and anatomic parameters in both acute myocardial infarction and chronic ischemic heart disease, above and beyond the conventional therapy. In particular, intracoronary application of BMC is proved to be safe and was associated with significant improvement in the left ventricular ejection fraction (LVEF) in patients with chronic heart failure. In contrast to ischemic heart failure, the data on effects of BMC transplantation in patients with dilated cardiomyopathy are limited to pre-clinical studies. In a rat model of dilated cardiomyopathy, intramyocardial delivery of pluripotent mesenchymal cells improved LVEF, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis, suggesting that the beneficial effects of stem cell transplantation in dilated cardiomyopathy may primarily be related to their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors. Similarly, transplantation of cocultured mesenchymal stem cells and skeletal myoblasts was shown to improve LVEF in a murine model of Chagas disease. Study Aim: To define the clinical effects of BMC transplantation in dilated cardiomyopathy in a pilot clinical study investigating the effects of intracoronary CD34+ cell transplantation on functional, structural, neurohormonal, and electrophysiologic parameters in patients with end-stage dilated cardiomyopathy.

Detailed Description
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Patients were randomly allocated in a 1:1 ratio to receive intracoronary transplantation of autologous CD34+ stem cells (SC group) or no intracoronary infusion (control group). At the time of enrollment, and at yearly intervals thereafter, we performed detailed clinical evaluation, echocardiography, 6-minute walk test, and measured plasma levels of NT-proBNP. To better-define the potential role of inflammatory response, we also measured plasma inflammatory markers (tumor necrosis factor [TNF]-α and interleukin [IL]-6) at the time of CD34+ stem cell injection.

Official Title
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The Effects of Autologous Intracoronary Stem Cell Transplantation In Patients With End-Stage Dilated Cardiomyopathy

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Biological: CD34+ autologous stem cell transplantation
* Drug: Bone Marrow Stimulation
* Biological: SC therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal coronary angiogram Left ventricular ejection fraction < 40% NYHA III or IV heart failure symptoms Bone marrow reactivity (G-CSF test) Presence of viable myocardium Exclusion Criteria: Hematologic malignancy Multiorgan failure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC Group<br>SC therapy,'Bone Marrow Stimulation','CD34+ autologous stem cell transplantation': In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect | Biological: CD34+ autologous stem cell transplantation<br>* Peripheral blood stem cells will be mobilized by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labeled with technetium. Patients will undergo myocardial perfusion scintigraphy for myocardial viability assessment and the collected CD34+ cells will be injected intracoronary in the artery supplying the segments of reduced tracer accumulation<br>Drug: Bone Marrow Stimulation<br>* Patients will undergo filgrastim stimulation and viability assessment using the same protocol as in Arm 1. However, in this group, no intracoronary stem cell delivery will be performed; the patients will receive placebo (saline).<br>* Other names: G-CSF stimulation;Biological: SC therapy<br>* In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect<br>|
| No Intervention: Controls<br>Patients receiving no cell therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Failure Mortality |  | 5 years | 
| Changes in Left Ventricular Ejection Fraction | Left ventricular ejection fraction measured by echocardiography | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Exercise Capacity |  | 5 years | 
| Changes in Electrophysiologic Properties of Ventricular Myocardium |  | 6 months | 
| Changes in Plasma Inflammatory Markers |  | 6 months | 
| Changes in Left Ventricular Function |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem Cells, Heart Failure, Dilated Cardiomyopathy