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

LVAD Therapy: Exploring the Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function

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; Biological: 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, 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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainsville, Florida, United States, 32610
      • University of Florida
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
  • 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
  • Texas
    • Dallas, Texas, United States, 75230
      • Baylor Research Institute
    • Houston, Texas, United States, 77030
      • Texas Heart Institute

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 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-human leukocyte antigen (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.

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
Sham Comparator: Control Solution; Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO	Biological: Control Solution; Injection of control solution during the LVAD implantation.; Other Names: Cryoprotective media
Experimental: MPC Intramyocardial injection; Intramyocardial injections of 25 million Mesenchymal Precursor Cells (MPCs)	Biological: MPC Intramyocardial injection; Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation; Other Names: RevascorTM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention Related Adverse Events	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.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Status and Ventricular Function	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. The number of participants who successfully tolerated the 30 minute wean from LVAD support at 90 days is reported.	90 days

Collaborators and Investigators

• Sponsor: Deborah Ascheim
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Timothy Gardner, MD, Christiana Care Health Services; Study Chair: Patrick O'Gara, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Ascheim DD, Gelijns AC, Goldstein D, Moye LA, Smedira N, Lee S, Klodell CT, Szady A, Parides MK, Jeffries NO, Skerrett D, Taylor DA, Rame JE, Milano C, Rogers JG, Lynch J, Dewey T, Eichhorn E, Sun B, Feldman D, Simari R, O'Gara PT, Taddei-Peters WC, Miller MA, Naka Y, Bagiella E, Rose EA, Woo YJ. Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation. 2014 Jun 3;129(22):2287-96. doi: 10.1161/CIRCULATIONAHA.113.007412. Epub 2014 Mar 28.

Helpful Links

• Cardiothoracic Surgical Network Website

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: September 26, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Heart Failure; Cell Therapy; Heart Transplantation; Cardiomyopathy; Left Ventricular Assist Device; Destination Therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiomyopathies; Ventricular Dysfunction
• Other Study ID Numbers: GCO 08-1078-00006; 711 (Ct Surgery Network Research Group); U01HL088942 (U.S. NIH Grant/Contract); U01HL088942-04 (U.S. NIH Grant/Contract)