The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in Patients Undergoing LVAD Implantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Deborah Ascheim, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01442129
First received: September 26, 2011
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow, and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.


Condition Intervention Phase
Heart Failure
Cardiomyopathy
Ventricular Dysfunction
Biological: Mesenchymal Precursor Cell Injection
Biological: 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: LVAD Therapy: Exploring the Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Intervention related adverse events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    The primary safety endpoint of this study is the incidence of the following potential study-intervention related adverse events within 90 days post intervention (LVAD implantation + intramyocardial injection of study product): infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization.


Secondary Outcome Measures:
  • Functional Status and Ventricular Function [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    The key efficacy endpoint of this study is functional status and ventricular function, while weaned from LVAD support, at 90 days post intervention (LVAD implantation + intramyocardial injection of study product). Functional status is defined by the ability to tolerate wean from LVAD support for 30 minutes without signs or symptoms of hypoperfusion, including, but not limited to symptoms of low output or signs of vascular congestion. Ventricular function will be assessed by transthoracic echocardiogram (TTE) in those patients able to be weaned for 30 minutes from LVAD support.


Enrollment: 30
Study Start Date: April 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MPC Intramyocardial injection
Intramyocardial injections of 25 million MPCs
Biological: Mesenchymal Precursor Cell Injection
Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation
Other Name: RevascorTM
Sham Comparator: Control Solution
Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
Biological: 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
Injection of control solution during the LVAD implantation.
Other Name: Cryoprotective media

Detailed Description:

Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced heart failure who are treated with left ventricular assist device (LVAD) implantation may result in a renewable source of proliferating functional cardiomyocytes, as well as induce development of capillaries and larger size blood vessels to supply oxygen and nutrients to endogenous myocardium and newly-implanted cardiomyocytes, and release factors capable of paracrine signaling. If safety is established and an efficacy signal is observed in this exploratory trial, then the investigators will design a follow-up trial (stage 2) based on an adaptive design. The next trial would randomize patients to active therapy at one of two doses (25 and 75 million MPCs) versus placebo, and based on a predetermined selection criterion drop randomization to one of the dose arms as results accrue. Should this exploratory trial demonstrate safety but no signal of efficacy, then the subsequent trial would be based on a single dose of 75 million MPCs versus placebo.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation;
  • Age 18 years or older;
  • If the subject 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 procedure;
  • Female subjects of childbearing potential must have a negative serum pregnancy test at screening;
  • Admitted to the clinical center at the time of randomization;
  • Clinical indication and accepted candidate for implantation of an FDA approved implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.

Exclusion Criteria:

  • Planned percutaneous LVAD implantation;
  • Anticipated requirement for biventricular mechanical support;
  • Cardiothoracic surgery within 30 days prior to randomization;
  • Myocardial infarction within 30 days prior to randomization;
  • Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty;
  • Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism);
  • Stroke within 30 days prior to randomization;
  • Platelet count < 100,000/ul within 24 hours prior to randomization;
  • Active systemic infection within 48 hours prior to randomization;
  • Presence of >10% anti-HLA antibody titers with known specificity to the MPC donor HLA antigens;
  • A 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);
  • Received investigational intervention within 30 days prior to randomization;
  • Treatment and/or an incompleted follow-up treatment of any investigational cell based therapy within 6 months prior to randomization;
  • Active participation in other research therapy for cardiovascular repair/regeneration;
  • Prior recipient of stem precursor cell therapy for cardiac repair;
  • Pregnant or breastfeeding at time of randomization.
  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: NCT01442129

Locations
United States, Florida
University of Florida
Gainsville, Florida, United States, 32610
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Montefiore Einstein Heart Center
Bronx, New York, United States, 10467
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor Research Institute
Dallas, Texas, United States, 75230
Texas Heart Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Deborah Ascheim
Investigators
Study Chair: Timothy Gardner, MD Christiana Care Health Services
Study Chair: Patrick O'Gara, MD Brigham and Women's Hospital
  More Information

Additional Information:
No publications provided by Mount Sinai School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Deborah Ascheim, Associate Professor, Clinical Director of Research, InCHOIR, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01442129     History of Changes
Other Study ID Numbers: GCO 08-1078-00006, U01HL088942, U01HL088942-04, 711
Study First Received: September 26, 2011
Last Updated: January 16, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Heart Failure
Left Ventricular Assist Device
Heart Transplantation
Cardiomyopathy
Destination Therapy
Cell Therapy

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 01, 2014