Clinical trial NCT00629018: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dilated Cardiomyopathy
Keywords: Stem Cells
Heart Failure
Dilated Cardiomyopathy
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Blood Transfusion Centre of Slovenia
name: Stanford University
First posted: 2008-03-05
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Heart Failure Mortality
timeFrame: 5 years
measure: Changes in Left Ventricular Ejection Fraction
timeFrame: 5 years
Secondary outcomes:
measure: Changes in Exercise Capacity
timeFrame: 5 years
measure: Changes in Electrophysiologic Properties of Ventricular Myocardium
timeFrame: 6 months
measure: Changes in Plasma Inflammatory Markers
timeFrame: 6 months
measure: Changes in Left Ventricular Function
timeFrame: 5 years
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Ljubljana University Medical Center
Study officials:
affiliation: Methodist DeBakey Heart Center, Houston TX, USA
name: Guillermo Torre Amione, MD, PhD
role: STUDY_DIRECTOR
affiliation: Stanford University
name: Francois Haddad, MD
role: STUDY_DIRECTOR
References:
citation: 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.