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

Heart Failure Clinical Trial

Official title:

The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Bridge to Transplant Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00927784
• Other study ID #: GCO 08-1093
• Secondary ID: P50HL077096
• Status: Terminated
• Phase: Phase 2
• Start date: August 2009
• Est. completion date: February 2011

Study information

• Verified date: February 2019
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: February 2011
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Biological:
• Mesenchymal Precursor cells (RevascorTM)
Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs (in sequential cohorts).

Drug:
• Cryoprotective media alone
Participants will receive intramyocardial injections of cryoprotective media (placebo).

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Angioblast Systems, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Infectious Myocarditis		Measured within 90 days of study entry
Primary	Incidence of Myocardial Rupture		Measured within 90 days of study entry
Primary	Incidence of Neoplasm		Measured within 90 days of study entry
Primary	Incidence of Hypersensitivity Reaction		Measured within 90 days of study entry
Primary	Incidence of Immune Sensitization		Measured within 90 days of study entry
Secondary	Assessment of LVAD Wean	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	up to 12 months
Secondary	Incidence of Study Intervention-related Adverse Events	This includes Device Malfunction-Pump Thrombus-Suspected and Internal Pump Component, Inflow, or Outflow Tract Infection	up to 12 months
Secondary	Incidence of All Serious Adverse Events		up to 12 months
Secondary	Number of Patients Who Experienced Donor-specific HLA Sensitization	Number of patients who experienced donor-specific HLA sensitization post-randomization in each treatment arm.	up to 12 months
Secondary	Incidence of Myocardial Neovascularization at Time of Explant		up to 12 months
Secondary	Incidence of Cardiomyocyte Regeneration at Explant		up to 12 months
Secondary	Incidence of Cell Engraftment and Fate at Explant		up to 12 months
Secondary	Incidence of Survival to Cardiac Transplantation		up to 12 months