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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00629018
Recruitment Status : Completed
First Posted : March 5, 2008
Results First Posted : May 12, 2015
Last Update Posted : May 12, 2015
Sponsor:
Collaborators:
Blood Transfusion Centre of Slovenia
Stanford University
Information provided by (Responsible Party):
Bojan Vrtovec, University Medical Centre Ljubljana

Tracking Information
First Submitted Date  ICMJE February 25, 2008
First Posted Date  ICMJE March 5, 2008
Results First Submitted Date  ICMJE April 9, 2013
Results First Posted Date  ICMJE May 12, 2015
Last Update Posted Date May 12, 2015
Study Start Date  ICMJE May 2006
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
  • Heart Failure Mortality [ Time Frame: 5 years ]
  • Changes in Left Ventricular Ejection Fraction [ Time Frame: 5 years ]
    Left ventricular ejection fraction measured by echocardiography
Original Primary Outcome Measures  ICMJE
 (submitted: February 25, 2008)		 Heart Failure Mortality [ Time Frame: 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
  • Changes in Exercise Capacity [ Time Frame: 5 years ]
  • Changes in Electrophysiologic Properties of Ventricular Myocardium [ Time Frame: 6 months ]
  • Changes in Plasma Inflammatory Markers [ Time Frame: 6 months ]
  • Changes in Left Ventricular Function [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2008)
  • Changes in Exercise Capacity [ Time Frame: 1 year ]
  • Changes in Electropysiologic Properties of Ventricular Myocardium [ Time Frame: 6 months ]
  • Changes in Plasma Inflammatory Markers [ Time Frame: 6 months ]
  • Changes in Left Ventricular Function [ Time Frame: 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Dilated Cardiomyopathy
Intervention  ICMJE
  • 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).
    Other Name: G-CSF stimulation
  • 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
Study Arms  ICMJE
  • Experimental: 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

    Interventions:
    • Biological: CD34+ autologous stem cell transplantation
    • Drug: Bone Marrow Stimulation
    • Biological: SC therapy
  • No Intervention: Controls
    Patients receiving no cell therapy.
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 23, 2015)		 110
Original Estimated Enrollment  ICMJE
 (submitted: February 25, 2008)		 50
Actual Study Completion Date  ICMJE April 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Slovenia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00629018
Other Study ID Numbers  ICMJE DCM-SCT1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Bojan Vrtovec, University Medical Centre Ljubljana
Original Responsible Party Peter Cernelc, Ljubljana University Medical Center
Current Study Sponsor  ICMJE University Medical Centre Ljubljana
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Blood Transfusion Centre of Slovenia
  • Stanford University
Investigators  ICMJE
Study Director: Guillermo Torre Amione, MD, PhD Methodist DeBakey Heart Center, Houston TX, USA
Study Director: Francois Haddad, MD Stanford University
PRS Account University Medical Centre Ljubljana
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP