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

NCT ID: NCT00629018

Last Updated: 2015-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2013-04-30

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.

Conditions

Dilated Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

SC Group

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

Group Type: EXPERIMENTAL

CD34+ autologous stem cell transplantation

Intervention Type: BIOLOGICAL

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

Bone Marrow Stimulation

Intervention Type: DRUG

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).

SC therapy

Intervention Type: BIOLOGICAL

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

Controls

Patients receiving no cell therapy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

CD34+ autologous stem cell transplantation

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

Intervention Type: BIOLOGICAL

Bone Marrow Stimulation

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).

Intervention Type: DRUG

SC therapy

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

Intervention Type: BIOLOGICAL

Other Intervention Names

G-CSF stimulation

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Blood Transfusion Centre of Slovenia

OTHER_GOV

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Bojan Vrtovec

prof. dr. Bojan vrtovec

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo Torre Amione, MD, PhD

Role: STUDY_DIRECTOR

Methodist DeBakey Heart Center, Houston TX, USA

Francois Haddad, MD

Role: STUDY_DIRECTOR

Stanford University

Locations

Ljubljana University Medical Center

Ljubljana, , Slovenia

Countries

Slovenia

References

Vrtovec B, Poglajen G, Sever M, Lezaic L, Domanovic D, Cernelc P, Haddad F, Torre-Amione G. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail. 2011 Apr;17(4):272-81. doi: 10.1016/j.cardfail.2010.11.007. Epub 2010 Dec 24.

Reference Type: DERIVED

PMID: 21440864 (View on PubMed)

Other Identifiers

DCM-SCT1

Identifier Type: -

Identifier Source: org_study_id