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

Phase 2

Completed

Conditions: Cardiomyopathy
Ventricular Dysfunction
Heart Failure

Interventions: Biological: MPC Intramyocardial Injection
Drug: Control Solution

Registration Number: NCT02362646

Lead Sponsor: Annetine Gelijns

Brief Summary: 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.

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; 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 159

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MPC Intramyocardial Injection	MPC Intramyocardial Injection	Intramyocardial injections of 150 million MPCs
Control Solution	Control Solution	Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO

Primary Outcome Measures

Name	Time	Method
Number of Temporary Weans From LVAD Support Tolerated	up to 6 months	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.
Number of Participants With Adverse Events	up to 6 months	Safety as assessed by number of study intervention-related adverse events

Secondary Outcome Measures

Name	Time	Method
Physiologic Assessments	up to 12 months	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)
Functional Status	up to 12 months	functional status, defined by the number of temporary weans from LVAD support tolerated
MCG Complex Figures	3 months and 12 months	Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Digit Span	3 months and 12 months	Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Digit Symbol Substitution Test	3 months and 12 months	Cognitive performance will be assessed using the Digit Symbol Substitution 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.
Change in Quality of Life (QoL)	6 months and 12 months	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.
Controlled Oral Word Association	3 months and 12 months	Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Overall Survival	up to 12 months
Histopathological Assessments of Myocardial Tissue	up to 12 months
Hopkins Verbal Learning Test	3 months and 12 months	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.
Trailmaking Tests A and B	3 months and 12 months	Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Hospital Costs	up to 12 months	Hospital resource use
Length of Stay	up to 12 months	Length of stay of index hospitalization
Hospitalizations	up to 12 months	Frequency and cause of readmissions

Trial Locations

Locations (19): Stanford University School of Medicine
🇺🇸
Stanford, California, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Duke University
🇺🇸
Durham, North Carolina, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Montefiore Einstein Heart Center
🇺🇸
Bronx, New York, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Baylor Research Institute
🇺🇸
Plano, Texas, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
University of Virginia Health Systems
🇺🇸
Charlottesville, Virginia, United States
University of Wisconsin School of Medicine and Public Health
🇺🇸
Madison, Wisconsin, United States
Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
🇨🇦
Québec City, Quebec, Canada
Toronto General Hospital
🇨🇦
Toronto, Ontario, Canada
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
University of Southern California
🇺🇸
Los Angeles, California, United States