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

Dilated Cardiomyopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00629018
• Other study ID #: DCM-SCT1
• Status: Completed
• Phase: Phase 2
• First received: February 25, 2008
• Last updated: April 23, 2015
• Start date: May 2006
• Est. completion date: April 2013

Study information

• Verified date: April 2015
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Health authority: Slovenia: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy

Intervention

Biological:
• 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

Drug:
• 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).

Biological:
• 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

Locations

Country	Name	City	State
Slovenia	Ljubljana University Medical Center	Ljubljana

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana	Blood Transfusion Centre of Slovenia, Stanford University

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart Failure Mortality		5 years	Yes
Primary	Changes in Left Ventricular Ejection Fraction	Left ventricular ejection fraction measured by echocardiography	5 years	No
Secondary	Changes in Exercise Capacity		5 years	No
Secondary	Changes in Electrophysiologic Properties of Ventricular Myocardium		6 months	Yes
Secondary	Changes in Plasma Inflammatory Markers		6 months	No
Secondary	Changes in Left Ventricular Function		5 years	No