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

• ClinicalTrials.gov Identifier: NCT01442129
• Recruitment Status: Completed
• First Posted: September 28, 2011
• Results First Posted: October 13, 2014
• Last Update Posted: May 1, 2015
• Sponsor: Deborah Ascheim
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Deborah Ascheim, Icahn School of Medicine at Mount Sinai

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Heart Failure; Cardiomyopathy; Ventricular Dysfunction	Biological: MPC Intramyocardial injection; Biological: Control Solution	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: LVAD Therapy: Exploring the Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function
• Study Start Date: April 2012
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
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 Name: RevascorTM
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 Name: Cryoprotective media

Outcome Measures

Primary Outcome Measures :

1. Intervention Related Adverse Events [ Time Frame: 90 days ]
   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.

Secondary Outcome Measures :

1. Functional Status and Ventricular Function [ Time Frame: 90 days ]

   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.

Eligibility Criteria

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

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 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.

Contacts and Locations

Locations

United States, Florida

University of Florida

Gainsville, Florida, United States, 32610

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Minnesota

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States, 55407

United States, New York

Montefiore Einstein Heart Center

Bronx, New York, United States, 10467

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Ohio State University

Columbus, Ohio, United States, 43210

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Baylor Research Institute

Dallas, Texas, United States, 75230

Texas Heart Institute

Houston, Texas, United States, 77030

Sponsors and Collaborators

Deborah Ascheim

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

More Information

Additional Information:

Cardiothoracic Surgical Network Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Deborah Ascheim, Associate Professor, Clinical Director of Research, InCHOIR, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01442129
• Other Study ID Numbers: GCO 08-1078-00006; U01HL088942 ( U.S. NIH Grant/Contract ); U01HL088942-04 ( U.S. NIH Grant/Contract ); 711 ( Other Identifier: Ct Surgery Network Research Group )
• First Posted: September 28, 2011
• Results First Posted: October 13, 2014
• Last Update Posted: May 1, 2015
• Last Verified: April 2015

Keywords provided by Deborah Ascheim, Icahn School of Medicine at Mount Sinai:

Heart Failure; Left Ventricular Assist Device; Heart Transplantation; Cardiomyopathy; Destination Therapy; Cell Therapy

Additional relevant MeSH terms:

Heart Failure; Cardiomyopathies; Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases