Clinical trial NCT02362646: Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Official title: Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Cardiomyopathy
Ventricular Dysfunction
Keywords: Heart Failure
Left Ventricular Assist Device
Heart Transplantation
Cardiomyopathy, Destination Therapy
Cell Therapy
Bridge to Transplant
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-02-13
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 (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

Primary outcomes:
measure: Number of Temporary Weans From LVAD Support Tolerated
timeFrame: up to 6 months
measure: Number of Participants With Adverse Events
timeFrame: up to 6 months
Secondary outcomes:
measure: Physiologic Assessments
timeFrame: up to 12 months
measure: Histopathological Assessments of Myocardial Tissue
timeFrame: up to 12 months
measure: Overall Survival
timeFrame: up to 12 months
measure: Change in Quality of Life (QoL)
timeFrame: 6 months and 12 months
measure: Hopkins Verbal Learning Test
timeFrame: 3 months and 12 months
measure: Trailmaking Tests A and B
timeFrame: 3 months and 12 months
measure: MCG Complex Figures
timeFrame: 3 months and 12 months
measure: Digit Span
timeFrame: 3 months and 12 months
measure: Digit Symbol Substitution Test
timeFrame: 3 months and 12 months
measure: Controlled Oral Word Association
timeFrame: 3 months and 12 months
measure: Length of Stay
timeFrame: up to 12 months
measure: Hospitalizations
timeFrame: up to 12 months
measure: Hospital Costs
timeFrame: up to 12 months
measure: Functional Status
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Bronx
country: United States
facility: Montefiore Einstein Heart Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Plano
country: United States
facility: Baylor Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health Systems
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Québec City
country: Canada
facility: Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
state: Quebec
Study officials:
affiliation: Brigham and Women's Hospital
name: Patrick O'Gara, MD
role: STUDY_CHAIR
affiliation: Toronto General Hospital
name: Richard Weisel, MD
role: STUDY_CHAIR
References:
citation: Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, Acker MA, Selzman CH, Soltesz EG, Kern JA, Maltais S, Charbonneau E, Pan S, Marks ME, Moquete EG, O'Sullivan KL, Taddei-Peters WC, McGowan LK, Green C, Rose EA, Jeffries N, Parides MK, Weisel RD, Miller MA, Hung J, O'Gara PT, Moskowitz AJ, Gelijns AC, Bagiella E, Milano CA; Cardiothoracic Surgical Trials Network. Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial. JAMA. 2019 Mar 26;321(12):1176-1186. doi: 10.1001/jama.2019.2341.