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

Brief Title

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

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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Heart Failure Mortality

Secondary Outcome

 Changes in Exercise Capacity

Condition

Dilated Cardiomyopathy

Intervention

CD34+ autologous stem cell transplantation

Study Arms / Comparison Groups

 SC 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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

110

Start Date

May 2006

Completion Date

April 2013

Primary Completion Date

April 2013

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
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Guillermo Torre Amione, MD, PhD, , 

Location Countries

Slovenia

Location Countries

Slovenia

NCT ID

NCT00629018

Organization ID

DCM-SCT1

Responsible Party

Principal Investigator

Study Sponsor

University Medical Centre Ljubljana

Collaborators

 Blood Transfusion Centre of Slovenia

Study Sponsor

Guillermo Torre Amione, MD, PhD, Study Director, Methodist DeBakey Heart Center, Houston TX, USA

Verification Date

April 2015