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

University Medical Centre Ljubljana

Status and phase: Completed; Phase 2

Conditions: Dilated Cardiomyopathy

Treatments: Biological: CD34+ autologous stem cell transplantation; Drug: Bone Marrow Stimulation; Biological: SC therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00629018

DCM-SCT1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

110 participants in 2 patient groups

SC Group

Experimental 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

Treatment:

Biological: SC therapy

Drug: Bone Marrow Stimulation

Biological: CD34+ autologous stem cell transplantation

Controls

No Intervention group

Description:

Patients receiving no cell therapy.