The TRansendocardial Stem Cell Injection Delivery Effects on Neomyogenesis STudy (The TRIDENT Study) — Trident  

Myocardial Infarction Clinical Trial

Official title: A Phase II, Randomized, Blinded, Study of the Safety and Efficacy of Transendocardial Injection of Allogeneic Human Mesenchymal Stem Cells (hMSCs) (20 Million or 100 Million Total MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction.

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Chronic Ischemic Left Ventricular Dysfunction
• Infarction
• Ischemia
• Myocardial Infarction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

• NCT number: NCT02013674
• Study type: Interventional
• Source: University of Miami
• Status: Completed
• Phase: Phase 2
• Start date: February 13, 2014
• Completion date: September 18, 2017