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

This study has been terminated.
(The enrollment has been terminated by the NHLBI for administrative reasons.)
Sponsor:
Collaborators:
Angioblast Systems
Information provided by (Responsible Party):
Deborah Ascheim, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00927784
First received: June 23, 2009
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Heart Failure
Biological: Mesenchymal Precursor cells (RevascorTM)
Drug: Cryoprotective media alone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Bridge to Transplant Patients

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, or immune sensitization [ Time Frame: Measured within 90 days of study entry ] [ Designated as safety issue: Yes ]
  • Incidence of myocardial rupture [ Time Frame: Measured within 90 days of study entry ] [ Designated as safety issue: Yes ]
  • Incidence of neoplasm [ Time Frame: Measured within 90 days of study entry ] [ Designated as safety issue: Yes ]
  • Incidence of hypersensitivity reaction [ Time Frame: Measured within 90 days of study entry ] [ Designated as safety issue: Yes ]
  • Incidence of immune sensitization [ Time Frame: Measured within 90 days of study entry ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of LVAD wean [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of all serious adverse events [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of anti-HLA antibody sensitization while on LVAD support [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of myocardial neovascularization at time of explant [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of cardiomyocyte regeneration at explant [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of cell engraftment and fate at explant [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of survival to cardiac transplantation [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: August 2009
Study Completion Date: February 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Cryoprotective media alone
Participants will receive intramyocardial injections of cryoprotective media alone (placebo).
Drug: Cryoprotective media alone
Participants will receive intramyocardial injections of cryoprotective media (placebo).
Other Name: placebo
Experimental: Mesenchymal Precursor cells (RevascorTM)
Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs in sequential cohorts.
Biological: Mesenchymal Precursor cells (RevascorTM)
Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs (in sequential cohorts).
Other Names:
  • Mesenchymal Precursor cells
  • RevascorTM

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00927784

Locations
United States, California
Sharp Memorial Hospital
San Diego, California, United States, 92123
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Illinois
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453
United States, Kentucky
Jewish Hospital
Louisville, Kentucky, United States, 40202
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55902
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Columbia University Medical Center
New York, New York, United States, 10032
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
United States, Utah
Intermountain Medical Center
Salt Lake City, Utah, United States, 84107
United States, Washington
Sacred Heart Medical Center
Spokane, Washington, United States, 99204
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Sponsors and Collaborators
Mount Sinai School of Medicine
Angioblast Systems
Investigators
Principal Investigator: Deborah Ascheim, MD Mount Sinai School of Medicine
Principal Investigator: Yoshifumi Naka, MD Columbia University
  More Information

No publications provided

Responsible Party: Deborah Ascheim, Associate Professor, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00927784     History of Changes
Other Study ID Numbers: GCO 08-1093, P50HL077096, P50 HL077096
Study First Received: June 23, 2009
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Mesenchymal Precursor Cells
Left Ventricular Assist Device
LVAD
Congestive Heart Failure
Stem Cells

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 31, 2014