Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Heart Function in People Receiving an LVAD

Phase 2

Terminated

Conditions: Heart Failure

Interventions: Drug: Cryoprotective media alone
Biological: Mesenchymal Precursor cells (RevascorTM)

Registration Number: NCT00927784

Lead Sponsor: Icahn School of Medicine at Mount Sinai

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

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
Known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products
History of cancer prior to screening (excluding basal cell carcinoma)
Acute or chronic infectious disease, including but not limited to human immunodeficiency virus (HIV)
Treatment and/or an incompleted follow-up treatment of any investigational therapy within 6 months of study entry
Active participation in other research therapy for cardiovascular repair/regeneration
Prior recipient of stem precursor cell therapy for cardiac repair
Pregnant or breastfeeding at the time of study entry

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cryoprotective media alone	Cryoprotective media alone	Participants will receive intramyocardial injections of cryoprotective media alone (placebo).
Mesenchymal Precursor cells (RevascorTM)	Mesenchymal Precursor cells (RevascorTM)	Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs in sequential cohorts.

Primary Outcome Measures

Name	Time	Method
Incidence of Hypersensitivity Reaction	Measured within 90 days of study entry
Incidence of Immune Sensitization	Measured within 90 days of study entry
Incidence of Myocardial Rupture	Measured within 90 days of study entry
Incidence of Neoplasm	Measured within 90 days of study entry
Incidence of Infectious Myocarditis	Measured within 90 days of study entry

Secondary Outcome Measures

Name	Time	Method
Incidence of All Serious Adverse Events	up to 12 months
Incidence of Cell Engraftment and Fate at Explant	up to 12 months
Assessment of LVAD Wean	up to 12 months	The secondary endpoints assessed during the LVAD wean include echocardiographic assessments, 6 minute walk, ability to tolerate wean from LVAD support, duration of ability to tolerate wean from LVAD support, and neuronal function. Measured at 60 days, 90 days, and every 60 days thereafter following LVAD implantation until heart transplantation or 12 months, whichever comes first
Incidence of Study Intervention-related Adverse Events	up to 12 months	This includes Device Malfunction-Pump Thrombus-Suspected and Internal Pump Component, Inflow, or Outflow Tract Infection
Number of Patients Who Experienced Donor-specific HLA Sensitization	up to 12 months	Number of patients who experienced donor-specific HLA sensitization post-randomization in each treatment arm.
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

Trial Locations

Locations (17): Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Sharp Memorial Hospital
🇺🇸
San Diego, California, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States
Advocate Christ Medical Center
🇺🇸
Oak Lawn, Illinois, United States
Jewish Hospital
🇺🇸
Louisville, Kentucky, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Sacred Heart Medical Center
🇺🇸
Spokane, Washington, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Intermountain Medical Center
🇺🇸
Salt Lake City, Utah, United States
St. Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States