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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Heart Failure, Cardiomyopathy, Ventricular Dysfunction

Intervention / Treatment
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* Biological: MPC Intramyocardial Injection
* Drug: Control Solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MPC Intramyocardial Injection<br>Intramyocardial injections of 150 million MPCs | Biological: MPC Intramyocardial Injection<br>* Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation<br>* Other names: RevascorTM;|
| Sham Comparator: Control Solution<br>Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO | Drug: Control Solution<br> <br> * Other names: Cryoprotective media;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Number of Participants With Adverse Events | Safety as assessed by number of study intervention-related adverse events | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Histopathological Assessments of Myocardial Tissue |  | up to 12 months | 
| Overall Survival |  | up to 12 months | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Length of Stay | Length of stay of index hospitalization | up to 12 months | 
| Hospitalizations | Frequency and cause of readmissions | up to 12 months | 
| Hospital Costs | Hospital resource use | up to 12 months | 
| Functional Status | functional status, defined by the number of temporary weans from LVAD support tolerated | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Left Ventricular Assist Device, Heart Transplantation, Cardiomyopathy, Destination Therapy, Cell Therapy, Bridge to Transplant