The TRansendocardial Stem Cell Injection Delivery Effects on Neomyogenesis STudy (The TRIDENT Study)
Condition: Chronic Ischemic Left Ventricular Dysfunction; Myocardial Infarction
MeSH terms: Myocardial Infarction; Ventricular Dysfunction; Ventricular Dysfunction, Left; Ischemia; Infarction
Study type: Interventional
Phase: Phase 2

Summary: 
      Thirty (30) patients with chronic ischemic left ventricular dysfunction secondary to MI
      scheduled to undergo cardiac catheterization will be enrolled in the study. This is a phase
      II study intended to gain additional safety and efficacy assessments among two dose levels
      previously studied in a phase I setting.
    

Detailed description: 
      Thirty (30) patients with chronic ischemic left ventricular dysfunction secondary to MI
      scheduled to undergo cardiac catheterization will be enrolled in the study.This is a phase II
      study intended to gain additional safety and efficacy assessments among two dose levels
      previously studied in a phase I setting. In this study, a 20 million total hMSC dose and a
      100 million total hMSC dose will be randomly allocated administered via the Biocardia Helical
      infusion system in a blinded manner.

      The technique of transplanting progenitor cells into a region of damaged myocardium, termed
      cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or
      repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be readily
      available, easy to culture to ensure adequate quantities for transplantation, and able to
      survive in host myocardium, which is 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 cardiomyocytes, embryonic stem cell-derived myocytes, tissue engineered contractile
      grafts9, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac
      precursors residing within the heart itself. 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 a 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.

      Chronic ischemic left ventricular dysfunction 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.
    

Intervention name(s): Allogeneic hMSCs
Intervention type(s): Biological
Intervention description(s): Allogeneic Adult Human Mesenchymal Stem Cells (MSCs) delivered via injection
Other intervention name(s): Allogeneic Adult Human Mesenchymal Stem Cells (MSCs)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cardiovascular; Chronic Ischemic Left Ventricular Dysfunction