The Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis Pilot Study (The POSEIDON-Pilot Study)
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; 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 grafts, 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 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 resulting from heart disease 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.
|Stem Cell Transplantation||Biological: Auto-hMSCs Biological: Allo-hMSCs||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction|
- Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation [ Time Frame: One month post-catheterization ]
- CT Infarct Size From Early Enhanced Defect: - Difference Between the Baseline and 13-month [ Time Frame: Baseline Month 13 post-catheterization ]Percentage change from 13-months post-catheterization to baseline.
- CT Measure of Left Ventricular Ejection Fraction [ Time Frame: Baseline Month 13 post-catheterization ]
- CT Measure of End Diastolic Volume [ Time Frame: Baseline Month 13 post-catheterization ]
- CT Measure of End Systolic Volume [ Time Frame: Baseline Month 13 post-catheterization ]
- CT Measure of Scar Size as % of LV Mass [ Time Frame: Baseline Month 13 post-catheterization ]
- Change in Distance Walked in 6-minutes From Baseline. [ Time Frame: 12-months ]
- Change in Minnesota Living With Heart Failure Total Score [ Time Frame: 12 months ]The Minnesota living with heart failure questionnaire uses a 6-point, zero to five, Likert scale. The total score is the sum of the 21 responses. The total score is considered the best measure of how heart failure and treatments impact a patients quality of life. The max score is 105, minimum score is 0. A lower score is considered a better quality of life.
- Change in New York Heart Association Class at 12-months [ Time Frame: 12 months ]
|Study Start Date:||March 2010|
|Study Completion Date:||October 2012|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Participants will receive an injection of 20 million, 100 million or 200 million autologous human mesenchymal stem cells.
Biological: Autologous human mesenchymal stem cells (Auto-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10^8 (20 million) Auto-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10^8 (100 million) Auto-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10^8 (200 million) Auto-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
Participants will receive an injection of 20 million, 100 million or 200 million allogeneic human mesenchymal stem cells.
Biological: Allogeneic human mesenchymal stem cells (Allo-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10^8 (20 million) Allo-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10^8 (100 million) Allo-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10^8 (200 million) Allo-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01087996
|United States, Florida|
|University of Miami Miller School of Medicine|
|Miami, Florida, United States|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States|
|Principal Investigator:||Joshua M Hare, MD||University of Miami|