Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Heart Function in People Receiving an LVAD

Study Overview
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Brief Summary
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Left ventricular assist devices (LVADs) are one treatment option for people with congestive heart failure. This study will evaluate the safety of injecting mesenchymal precursor cells (MPCs) into the heart during LVAD implantation surgery and examine if injecting MPCs into the heart is effective at improving heart function.

Detailed Description
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Congestive heart failure is a major health problem and recent estimates indicate that end-stage heart failure with a 2-year mortality rate of 70-80% affects over 60,000 people in the United States each year. For these patients, treatment options are extremely limited. Less than 3,000 heart transplants are available each year because of the severely limited supply of donor hearts. Implantable LVADs, routinely used to support heart transplantation patients who decompensate awaiting a donor heart, were approved by the Food and Drug Administration (FDA) in 2002 for long-term support when heart transplantation is not an option. Few patients, however, achieve sufficient recovery to warrant LVAD explantation and those who do must still contend with ventricular dysfunction. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells. The purpose of this study is to determine the safety of injecting MPCs into the heart during LVAD implantation surgery. In addition, this study will examine whether injecting MPCs into the heart is effective at improving heart function. This study will enroll people who are on the waiting list to receive a donor heart and who are undergoing LVAD implantation surgery. Before the surgery, participants will be randomly assigned to one of two groups. One group of participants will have MPCs injected into their heart during LVAD surgery and the other group of participants will have a control solution (placebo) injected into their heart during the surgery. A portion of heart muscle removed during the surgery will be analyzed. Participants will be monitored by study researchers and blood samples will be collected 12 hours after the LVAD surgery and at 1, 7, 21, 60, and 90 days after the surgery. After that, a medical history review, physical examination, and blood collection will occur every 60 days until a heart transplant occurs or until 12 months after the LVAD implantation, whichever comes first. Heart function testing, which will include an echocardiogram, neuronal function testing, and a 6-minute walk test, will occur 60 and 90 days after the LVAD implantation, and every 2 months thereafter until a heart transplant occurs or until 12 months after the LVAD implantation, whichever comes first.

Official Title
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The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Bridge to Transplant Patients

Conditions
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Heart Failure

Intervention / Treatment
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* Biological: Mesenchymal Precursor cells (RevascorTM)
* Drug: Cryoprotective media alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent, release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documents Age 18 years or older If the participant 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 LVAD implantation Female participants of childbearing potential must have a negative serum pregnancy test at screening Admitted to the clinical center at the time of study entry Listed with the United Network for Organ Sharing (UNOS) for heart transplantation Clinical indication and accepted candidate for implantation of an FDA- approved LVAD as a bridge to transplantation Exclusion Criteria: Cardiothoracic surgery within 30 days of study entry Heart attack within 30 days of study entry Prior heart transplantation, left ventricular (LV) reduction surgery, or cardiomyoplasty Acute reversible cause of heart failure (e.g., myocarditis, profound hypothyroidism) Anticipated requirement for biventricular mechanical support Stroke within 30 days of study entry Received investigational intervention within 30 days of study entry Platelet count less than 100,000/uL within 24 hours of study entry Active systemic infection within 48 hours of study entry Presence of greater than 10% anti-human leukocyte antigen (HLA) antibody titers with known specificity to the MPC donor HLA antigens 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) Treatment and/or an incompleted follow-up treatment of any investigational therapy within 6 months of study entry Active participation in other research therapy for cardiovascular repair/regeneration Prior recipient of stem precursor cell therapy for cardiac repair Pregnant or breastfeeding at the time of study entry

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Cryoprotective media alone<br>Participants will receive intramyocardial injections of cryoprotective media alone (placebo). | Drug: Cryoprotective media alone<br>* Participants will receive intramyocardial injections of cryoprotective media (placebo).<br>* Other names: placebo;|
| Experimental: Mesenchymal Precursor cells (RevascorTM)<br>Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs in sequential cohorts. | Biological: Mesenchymal Precursor cells (RevascorTM)<br>* Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs (in sequential cohorts).<br>* Other names: RevascorTM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Infectious Myocarditis |  | Measured within 90 days of study entry | 
| Incidence of Myocardial Rupture |  | Measured within 90 days of study entry | 
| Incidence of Neoplasm |  | Measured within 90 days of study entry | 
| Incidence of Hypersensitivity Reaction |  | Measured within 90 days of study entry | 
| Incidence of Immune Sensitization |  | Measured within 90 days of study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of LVAD Wean | The secondary endpoints assessed during the LVAD wean include echocardiographic assessments, 6 minute walk, ability to tolerate wean from LVAD support, duration of ability to tolerate wean from LVAD support, and neuronal function. Measured at 60 days, 90 days, and every 60 days thereafter following LVAD implantation until heart transplantation or 12 months, whichever comes first | up to 12 months | 
| Incidence of Study Intervention-related Adverse Events | This includes Device Malfunction-Pump Thrombus-Suspected and Internal Pump Component, Inflow, or Outflow Tract Infection | up to 12 months | 
| Incidence of All Serious Adverse Events |  | up to 12 months | 
| Number of Patients Who Experienced Donor-specific HLA Sensitization | Number of patients who experienced donor-specific HLA sensitization post-randomization in each treatment arm. | up to 12 months | 
| Incidence of Myocardial Neovascularization at Time of Explant |  | up to 12 months | 
| Incidence of Cardiomyocyte Regeneration at Explant |  | up to 12 months | 
| Incidence of Cell Engraftment and Fate at Explant |  | up to 12 months | 
| Incidence of Survival to Cardiac Transplantation |  | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Precursor Cells, Left Ventricular Assist Device, LVAD, Congestive Heart Failure, Stem Cells