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

NCT ID: NCT01442129

Last Updated: 2015-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2013-08-31

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, 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.

Conditions

Heart Failure; Cardiomyopathy; Ventricular Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MPC Intramyocardial injection

Intramyocardial injections of 25 million Mesenchymal Precursor Cells (MPCs)

Group Type: EXPERIMENTAL

MPC Intramyocardial injection

Intervention Type: BIOLOGICAL

Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation

Control Solution

Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO

Group Type: SHAM_COMPARATOR

Control Solution

Intervention Type: BIOLOGICAL

Injection of control solution during the LVAD implantation.

Interventions

MPC Intramyocardial injection

Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation

Intervention Type: BIOLOGICAL

Control Solution

Injection of control solution during the LVAD implantation.

Intervention Type: BIOLOGICAL

Other Intervention Names

RevascorTM; Cryoprotective media

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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Deborah Ascheim

OTHER

Sponsor Role: lead

Responsible Party

Deborah Ascheim

Associate Professor, Clinical Director of Research, InCHOIR

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Timothy Gardner, MD

Role: STUDY_CHAIR

Christiana Care Health Services

Patrick O'Gara, MD

Role: STUDY_CHAIR

Brigham and Women's Hospital

Locations

University of Florida

Gainsville, Florida, United States

University of Maryland

Baltimore, Maryland, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Einstein Heart Center

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor Research Institute

Dallas, Texas, United States

Texas Heart Institute

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24682346 (View on PubMed)

Related Links

http://www.ctsurgerynet.org/

Cardiothoracic Surgical Network Website

Other Identifiers

U01HL088942

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL088942-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

711

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 08-1078-00006

Identifier Type: -

Identifier Source: org_study_id