Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients

Heart Failure Clinical Trial

Official title:

Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02362646
• Other study ID #: GCO 08-1078-0008
• Secondary ID: 2U01HL088942-07
• Status: Completed
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: August 23, 2019

Study information

• Verified date: November 2019
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• 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; 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: August 23, 2019
• Est. primary completion date: August 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• 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 (US sites only) or Health Canada-approved (Canadian sites only) 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

• Concomitant arrhythmia ablation at time of LVAD implantation

-- Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation

• Cardiothoracic surgery within 30 days prior to randomization

• Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as unstable plaque rupture, erosion or dissection 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

• Acute infectious process: acute bacterial, fungal, or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis

• Presence of >10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens

• A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products

• History of a known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated

• Presence of human immunodeficiency virus (HIV)

• Received investigational intervention within 30 days prior to randomization

• Treatment and/or an incomplete 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.

• History of known or suspected hypercoagulable state in the opinion of the investigator

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Heart Failure
• Ventricular Dysfunction

Intervention

Biological:
• MPC Intramyocardial Injection
Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation

Drug:
• Control Solution

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Institut Universitaire de Cardiologie de Quebec (Hopital Laval)	Québec City	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Maryland	Baltimore	Maryland
United States	Montefiore Einstein Heart Center	Bronx	New York
United States	University of Virginia Health Systems	Charlottesville	Virginia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	University of Southern California	Los Angeles	California
United States	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Baylor Research Institute	Plano	Texas
United States	University of Utah	Salt Lake City	Utah
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Annetine Gelijns	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Temporary Weans From LVAD Support Tolerated	functional status, defined by the number of temporary weans from LVAD support tolerated over the 6 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt.	up to 6 months
Primary	Number of Participants With Adverse Events	Safety as assessed by number of study intervention-related adverse events	up to 6 months
Secondary	Physiologic Assessments	Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes)	up to 12 months
Secondary	Histopathological Assessments of Myocardial Tissue		up to 12 months
Secondary	Overall Survival		up to 12 months
Secondary	Change in Quality of Life (QoL)	Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure.	6 months and 12 months
Secondary	Hopkins Verbal Learning Test	Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.	3 months and 12 months
Secondary	Trailmaking Tests A and B	Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.	3 months and 12 months
Secondary	MCG Complex Figures	Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.	3 months and 12 months
Secondary	Digit Span	Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.	3 months and 12 months
Secondary	Digit Symbol Substitution Test	Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.	3 months and 12 months
Secondary	Controlled Oral Word Association	Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.	3 months and 12 months
Secondary	Length of Stay	Length of stay of index hospitalization	up to 12 months
Secondary	Hospitalizations	Frequency and cause of readmissions	up to 12 months
Secondary	Hospital Costs	Hospital resource use	up to 12 months
Secondary	Functional Status	functional status, defined by the number of temporary weans from LVAD support tolerated	up to 12 months

External Links

•   Cardiothoracic Surgical Network Website