Brief Title
Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
Official Title
The Effects of Autologous Intracoronary Stem Cell Transplantation In Patients With End-Stage Dilated Cardiomyopathy
Brief Summary
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Heart Failure Mortality
Secondary Outcome
Changes in Exercise Capacity
Condition
Dilated Cardiomyopathy
Intervention
CD34+ autologous stem cell transplantation
Study Arms / Comparison Groups
SC Group
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
110
Start Date
May 2006
Completion Date
April 2013
Primary Completion Date
April 2013
Eligibility Criteria
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
Gender
All
Ages
18 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Guillermo Torre Amione, MD, PhD, ,
Location Countries
Slovenia
Location Countries
Slovenia
Administrative Informations
NCT ID
NCT00629018
Organization ID
DCM-SCT1
Responsible Party
Principal Investigator
Study Sponsor
University Medical Centre Ljubljana
Collaborators
Blood Transfusion Centre of Slovenia
Study Sponsor
Guillermo Torre Amione, MD, PhD, Study Director, Methodist DeBakey Heart Center, Houston TX, USA
Verification Date
April 2015