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

Phase 2

Completed

• Conditions: Dilated Cardiomyopathy
• Interventions: Biological: CD34+ autologous stem cell transplantation; Drug: Bone Marrow Stimulation; Biological: SC therapy

• Registration Number: NCT00629018
• Lead Sponsor: University Medical Centre Ljubljana

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 Timeline

• Study Start: 2006-05
• Study First Submitted: 2008-02-25
• Study First Submitted QC: 2008-02-25
• Study First Posted: 2008-03-05
• Primary Completion: 2013-04
• Study Completion: 2013-04
• Results First Submitted: 2013-04-09
• Status Verified: 2015-04
• Results First Submitted QC: 2015-04-23
• Last Update Submitted: 2015-04-23
• Results First Posted: 2015-05-12
• Last Update Posted: 2015-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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

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Exclusion Criteria

• Hematologic malignancy
• Multiorgan failure

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SC Group	SC therapy	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
SC Group	CD34+ autologous stem cell transplantation	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
SC Group	Bone Marrow Stimulation	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

Primary Outcome Measures

Name	Time	Method
Heart Failure Mortality	5 years
Changes in Left Ventricular Ejection Fraction	5 years	Left ventricular ejection fraction measured by echocardiography

Secondary Outcome Measures

Name	Time	Method
Changes in Electrophysiologic Properties of Ventricular Myocardium	6 months
Changes in Plasma Inflammatory Markers	6 months
Changes in Exercise Capacity	5 years
Changes in Left Ventricular Function	5 years

Trial Locations

Locations (1)

Ljubljana University Medical Center; 🇸🇮 Ljubljana, Slovenia