Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients

Annetine Gelijns159 enrolled

Overview

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.

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; 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

159

Conditions

Heart Failure Cardiomyopathy Ventricular Dysfunction

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 (US sites only) or Health Canada-approved (Canadian sites only) 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 * Concomitant arrhythmia ablation at time of LVAD implantation \-- Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation * Cardiothoracic surgery within 30 days prior to randomization * Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as unstable plaque rupture, erosion or dissection 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 * Acute infectious process: acute bacterial, fungal, or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis * Presence of \>10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens * A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products * History of a known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated * Presence of human immunodeficiency virus (HIV) * Received investigational intervention within 30 days prior to randomization * Treatment and/or an incomplete 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. * History of known or suspected hypercoagulable state in the opinion of the investigator

Locations (19)

University of Southern California

Los Angeles, California, United States

Stanford University School of Medicine

Stanford, California, United States

University of Maryland

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Einstein Heart Center

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

...and 9 more locations

Outcomes

Primary Outcomes

Number of Temporary Weans From LVAD Support Tolerated

functional status, defined by the number of temporary weans from LVAD support tolerated over the 6 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt.

Time frame: up to 6 months

Number of Participants With Adverse Events

Safety as assessed by number of study intervention-related adverse events

Time frame: up to 6 months

Secondary Outcomes

Physiologic Assessments

Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes)

Time frame: up to 12 months

Histopathological Assessments of Myocardial Tissue

Time frame: up to 12 months

Overall Survival

Time frame: up to 12 months

Change in Quality of Life (QoL)

Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure.

Time frame: 6 months and 12 months

Hopkins Verbal Learning Test

Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.