Clinical trial NCT00927784: Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Heart Function in People Receiving an LVAD
Official title: The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Bridge to Transplant Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Mesenchymal Precursor Cells
Left Ventricular Assist Device
LVAD
Congestive Heart Failure
Stem Cells
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Angioblast Systems
First posted: 2009-06-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: Incidence of Infectious Myocarditis
timeFrame: Measured within 90 days of study entry
measure: Incidence of Myocardial Rupture
timeFrame: Measured within 90 days of study entry
measure: Incidence of Neoplasm
timeFrame: Measured within 90 days of study entry
measure: Incidence of Hypersensitivity Reaction
timeFrame: Measured within 90 days of study entry
measure: Incidence of Immune Sensitization
timeFrame: Measured within 90 days of study entry
Secondary outcomes:
measure: Assessment of LVAD Wean
timeFrame: up to 12 months
measure: Incidence of Study Intervention-related Adverse Events
timeFrame: up to 12 months
measure: Incidence of All Serious Adverse Events
timeFrame: up to 12 months
measure: Number of Patients Who Experienced Donor-specific HLA Sensitization
timeFrame: up to 12 months
measure: Incidence of Myocardial Neovascularization at Time of Explant
timeFrame: up to 12 months
measure: Incidence of Cardiomyocyte Regeneration at Explant
timeFrame: up to 12 months
measure: Incidence of Cell Engraftment and Fate at Explant
timeFrame: up to 12 months
measure: Incidence of Survival to Cardiac Transplantation
timeFrame: up to 12 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Spokane
country: United States
facility: Sacred Heart Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Deborah Ascheim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Yoshifumi Naka, MD
role: PRINCIPAL_INVESTIGATOR
References: