Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
Condition: Dilated Cardiomyopathy
MeSH terms: Cardiomyopathies; Cardiomyopathy, Dilated
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): CD34+ autologous stem cell transplantation; Bone Marrow Stimulation; SC therapy
Intervention type(s): Biological; Drug; Biological
Intervention description(s): 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; 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).; 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
Other intervention name(s): G-CSF stimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Stem Cells; Heart Failure; Dilated Cardiomyopathy