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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Ventricular Dysfunction; Cardiomyopathy
• Intervention / Treatment: Biological: MPC Intramyocardial Injection; Drug: Control Solution

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.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Québec City, Quebec, Canada, G1V 4G5
      • Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Einstein Heart Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Plano, Texas, United States, 75093
      • Baylor Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health Systems
  • Wisconsin
    • Madison, Wisconsin, United States, 53726
      • University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MPC Intramyocardial Injection; Intramyocardial injections of 150 million MPCs	Biological: MPC Intramyocardial Injection; Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation; Other Names: Mesenchymal Precursor Cell Injection; RevascorTM
Sham Comparator: Control Solution; Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO	Drug: Control Solution; Other Names: 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO; Cryoprotective media

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6 months
Number of Participants With Adverse Events	Safety as assessed by number of study intervention-related adverse events	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		up to 12 months
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)	up to 12 months
Histopathological Assessments of Myocardial Tissue		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.	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.	3 months and 12 months
Trailmaking Tests A and B	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.	3 months and 12 months
MCG Complex Figures	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.	3 months and 12 months
Digit Span	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.	3 months and 12 months
Digit Symbol Substitution Test	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.	3 months and 12 months
Controlled Oral Word Association	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.	3 months and 12 months
Length of Stay	Length of stay of index hospitalization	up to 12 months
Hospitalizations	Frequency and cause of readmissions	up to 12 months
Hospital Costs	Hospital resource use	up to 12 months
Functional Status	functional status, defined by the number of temporary weans from LVAD support tolerated	up to 12 months

Collaborators and Investigators

• Sponsor: Annetine Gelijns
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Patrick O'Gara, MD, Brigham and Women's Hospital; Study Chair: Richard Weisel, MD, Toronto General Hospital

Publications and helpful links

General Publications

• 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. Erratum In: JAMA. 2019 Sep 3;322(9):895.

Helpful Links

• Cardiothoracic Surgical Network Website

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): August 10, 2018
• Study Completion (Actual): August 23, 2019

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 12, 2015
• First Posted (Estimate): February 13, 2015

Study Record Updates

• Last Update Posted (Actual): November 26, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Heart Failure; Cell Therapy; Heart Transplantation; Left Ventricular Assist Device; Bridge to Transplant; Cardiomyopathy, Destination Therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiomyopathies; Ventricular Dysfunction
• Other Study ID Numbers: GCO 08-1078-0008; 2U01HL088942-07 (U.S. NIH Grant/Contract)