Clinical trial NCT01442129: The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in Patients Undergoing LVAD Implantation
Official title: LVAD Therapy: Exploring the Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Cardiomyopathy
Ventricular Dysfunction
Keywords: Heart Failure
Left Ventricular Assist Device
Heart Transplantation
Cardiomyopathy
Destination Therapy
Cell Therapy
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-09-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Intervention Related Adverse Events
timeFrame: 90 days
Secondary outcomes:
measure: Functional Status and Ventricular Function
timeFrame: 90 days
Other outcomes:
Locations:
city: Gainsville
country: United States
facility: University of Florida
state: Florida
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Einstein Heart Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
Study officials:
affiliation: Christiana Care Health Services
name: Timothy Gardner, MD
role: STUDY_CHAIR
affiliation: Brigham and Women's Hospital
name: Patrick O'Gara, MD
role: STUDY_CHAIR
References:
citation: 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.