The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Bridge to Transplant Patients
Overview
- Phase
- Phase 2
- Intervention
- Cryoprotective media alone
- Conditions
- Heart Failure
- Sponsor
- Icahn School of Medicine at Mount Sinai
- Enrollment
- 10
- Locations
- 17
- Primary Endpoint
- Incidence of Myocardial Rupture
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
Left ventricular assist devices (LVADs) are one treatment option for people with congestive heart failure. This study will evaluate the safety of injecting mesenchymal precursor cells (MPCs) into the heart during LVAD implantation surgery and examine if injecting MPCs into the heart is effective at improving heart function.
Detailed Description
Congestive heart failure is a major health problem and recent estimates indicate that end-stage heart failure with a 2-year mortality rate of 70-80% affects over 60,000 people in the United States each year. For these patients, treatment options are extremely limited. Less than 3,000 heart transplants are available each year because of the severely limited supply of donor hearts. Implantable LVADs, routinely used to support heart transplantation patients who decompensate awaiting a donor heart, were approved by the Food and Drug Administration (FDA) in 2002 for long-term support when heart transplantation is not an option. Few patients, however, achieve sufficient recovery to warrant LVAD explantation and those who do must still contend with ventricular dysfunction. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells. The purpose of this study is to determine the safety of injecting MPCs into the heart during LVAD implantation surgery. In addition, this study will examine whether injecting MPCs into the heart is effective at improving heart function. This study will enroll people who are on the waiting list to receive a donor heart and who are undergoing LVAD implantation surgery. Before the surgery, participants will be randomly assigned to one of two groups. One group of participants will have MPCs injected into their heart during LVAD surgery and the other group of participants will have a control solution (placebo) injected into their heart during the surgery. A portion of heart muscle removed during the surgery will be analyzed. Participants will be monitored by study researchers and blood samples will be collected 12 hours after the LVAD surgery and at 1, 7, 21, 60, and 90 days after the surgery. After that, a medical history review, physical examination, and blood collection will occur every 60 days until a heart transplant occurs or until 12 months after the LVAD implantation, whichever comes first. Heart function testing, which will include an echocardiogram, neuronal function testing, and a 6-minute walk test, will occur 60 and 90 days after the LVAD implantation, and every 2 months thereafter until a heart transplant occurs or until 12 months after the LVAD implantation, whichever comes first.
Investigators
Annetine Gelijns
Associate Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent, release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documents
- •Age 18 years or older
- •If the participant or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after LVAD implantation
- •Female participants of childbearing potential must have a negative serum pregnancy test at screening
- •Admitted to the clinical center at the time of study entry
- •Listed with the United Network for Organ Sharing (UNOS) for heart transplantation
- •Clinical indication and accepted candidate for implantation of an FDA- approved LVAD as a bridge to transplantation
Exclusion Criteria
- •Cardiothoracic surgery within 30 days of study entry
- •Heart attack within 30 days of study entry
- •Prior heart transplantation, left ventricular (LV) reduction surgery, or cardiomyoplasty
- •Acute reversible cause of heart failure (e.g., myocarditis, profound hypothyroidism)
- •Anticipated requirement for biventricular mechanical support
- •Stroke within 30 days of study entry
- •Received investigational intervention within 30 days of study entry
- •Platelet count less than 100,000/uL within 24 hours of study entry
- •Active systemic infection within 48 hours of study entry
- •Presence of greater than 10% anti-human leukocyte antigen (HLA) antibody titers with known specificity to the MPC donor HLA antigens
Arms & Interventions
Cryoprotective media alone
Participants will receive intramyocardial injections of cryoprotective media alone (placebo).
Intervention: Cryoprotective media alone
Mesenchymal Precursor cells (RevascorTM)
Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs in sequential cohorts.
Intervention: Mesenchymal Precursor cells (RevascorTM)
Outcomes
Primary Outcomes
Incidence of Myocardial Rupture
Time Frame: Measured within 90 days of study entry
Incidence of Neoplasm
Time Frame: Measured within 90 days of study entry
Incidence of Hypersensitivity Reaction
Time Frame: Measured within 90 days of study entry
Incidence of Immune Sensitization
Time Frame: Measured within 90 days of study entry
Incidence of Infectious Myocarditis
Time Frame: Measured within 90 days of study entry
Secondary Outcomes
- Assessment of LVAD Wean(up to 12 months)
- Incidence of Study Intervention-related Adverse Events(up to 12 months)
- Incidence of All Serious Adverse Events(up to 12 months)
- Incidence of Cell Engraftment and Fate at Explant(up to 12 months)
- Number of Patients Who Experienced Donor-specific HLA Sensitization(up to 12 months)
- Incidence of Myocardial Neovascularization at Time of Explant(up to 12 months)
- Incidence of Cardiomyocyte Regeneration at Explant(up to 12 months)
- Incidence of Survival to Cardiac Transplantation(up to 12 months)