PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis in Dilated CardioMyopathy (The POSEIDON-DCM Study)
Condition: Non-ischemic Dilated Cardiomyopathy
MeSH terms: Cardiomyopathies; Cardiomyopathy, Dilated
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The technique of transplanting progenitor cells into a region of damaged myocardium, termed
      cellular cardiomyoplasty1, is a potentially new therapeutic modality designed to replace or
      repair necrotic, scarred, or dysfunctional myocardium2-4. Ideally, graft cells should be
      readily available, easy to culture to ensure adequate quantities for transplantation, and
      able to survive in host myocardium; often a hostile environment of limited blood supply and
      immunorejection. Whether effective cellular regenerative strategies require that administered
      cells differentiate into adult cardiomyocytes and couple electromechanically with the
      surrounding myocardium is increasingly controversial and recent evidence suggests that this
      may not be required for effective cardiac repair. Most importantly, transplantation of graft
      cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a
      number of candidate cells have been transplanted in experimental models, including fetal and
      neonatal cardiomyocytes5, embryonic stem cell-derived myocytes6, 7, tissue engineered
      contractile grafts8, skeletal myoblasts9, several cell types derived from adult bone
      marrow10-15, and cardiac precursors residing within the heart itself16. There has been
      substantial clinical development in the use of whole bone marrow and skeletal myoblast
      preparations in studies enrolling both post-infarction patients, and patients with chronic
      ischemic left ventricular dysfunction and heart failure. The effects of bone-marrow derived
      mesenchymal stem cells (MSCs) have also been studied clinically.

      Currently, bone marrow or bone marrow-derived cells represent highly promising modality for
      cardiac repair. The totality of evidence from trials investigating autologous whole bone
      marrow infusions into patients following myocardial infarction supports the safety of this
      approach. In terms of efficacy, increases in ejection fraction are reported in the majority
      of the trials.

      Non-ischemic dilated cardiomyopathy is a common and problematic condition; definitive therapy
      in the form of heart transplantation is available to only a tiny minority of eligible
      patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for
      acute MI, but represents a potentially important alternative for this disease.
    

Detailed description: 
      This is a Pilot Study, intended as a safety assessment prior to a full comparator study. In
      this Pilot Study, cells administered via the Biosense Webster MyoStar NOGA injection catheter
      system will be tested in 36 patients in two groups:

      Group 1 (18 patients) Eighteen (18) patients will be treated with Auto-hMSCs: 20 million
      cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 X 108
      (100 million) Auto-hMSCs.

      Group 2 (18 patients) Eighteen (18) patients will be treated with Allo-hMSCs: 20 million
      cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 X 108
      (100 million) Auto-hMSCs.

      The first three (3) patients in each group (Group 1 and Group 2) will not be treated less
      than 5 days apart and will each undergo full evaluation for 5 days to demonstrate there is no
      evidence of a procedure induced myocardial infarction or myocardial perforation prior to
      proceeding with the treatment of further patients.

      Patients will be randomized in a 1:1 ratio to one of the two groups.

      Treatment Strategies: Autologous hMSCs vs. Allogeneic hMSCs. The Study Team will record and
      maintain a detailed record of injection locations.

      If a patient is randomized to Groups 1 (Auto-hMSCs) and the Auto-hMSCs do not expand to the
      required dose of 1 X 108 cells, each injection will contain the maximum number of cells
      available.

      The injections will be administered transendocardially during cardiac catheterization using
      the Biosense Webster MyoStar NOGA Catheter System.

      For patients randomized to Group 1(Auto-hMSCs); the cells will be derived from a sample of
      the patient's bone marrow (obtained by iliac crest aspiration) approximately 4-6 weeks prior
      to cardiac catheterization. For patients randomized to Group 2 (Allo- hMSCs), the cells will
      be supplied from an allogeneic human mesenchymal stem cell source manufactured by the
      University of Miami. The Allo-hMSCs for patients in group 2 will be administered after all
      baseline assessments are completed with an expected range of 2 - 4 weeks post-randomization.

      Following cardiac catheterization and cell injections, patients will be hospitalized for a
      minimum of 2 days then followed at 2 weeks post-catheterization, and at month 2, 3, 6, and 12
      to complete all safety and efficacy assessments.
    

Intervention name(s): Autologous hMSCs; Allogeneic hMSCs
Intervention type(s): Biological; Biological
Intervention description(s): Cells will be administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested in 18 patients via transendocardial injection:
Group 1 (18 patients) Eighteen (18) patients will be treated with Auto-hMSCs: 20 million cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 x 108 (100 million) Auto-hMSCs.; Cells will be administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested in 18 patients via transendocardial injection:
Group 2 (18 patients) Eighteen (18) patients will be treated with Allo-hMSCs: 20 million cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 x 108 (100 million) Auto-hMSCs.
Other intervention name(s): Biosense Webster MyoStar NOGA Injection Catheter System.; Biosense Webster MyoStar NOGA Injection Catheter System.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Non ischemic dilated cardiomyopathy; Dilated cardiomyopathy; Heart failure; Cardiac Stem Cell Transplantation; Stem Cells