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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01442129
• Other study ID #: GCO 08-1078-00006
• Secondary ID: U01HL088942U01HL
• Status: Completed
• Phase: Phase 2
• First received: September 26, 2011
• Last updated: April 10, 2015
• Start date: April 2012
• Est. completion date: August 2013

Study information

• Verified date: April 2015
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Heart Failure
• Ventricular Dysfunction

Intervention

Biological:
• MPC Intramyocardial injection
Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation
• Control Solution
Injection of control solution during the LVAD implantation.

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	Montefiore Einstein Heart Center	Bronx	New York
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor Research Institute	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	University of Florida	Gainsville	Florida
United States	Texas Heart Institute	Houston	Texas
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Deborah Ascheim	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No

External Links

•   Cardiothoracic Surgical Network Website