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.
Brief Title
Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
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; 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Heart Failure
Cardiomyopathy
Ventricular Dysfunction
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 (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
* 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
Inclusion 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 (US sites only) or Health Canada-approved (Canadian sites only) implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.
* 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.
Gender
All
Gender Based
false
Keywords
Heart Failure
Left Ventricular Assist Device
Heart Transplantation
Cardiomyopathy, Destination Therapy
Cell Therapy
Bridge to Transplant
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02362646
Org Class
Other
Org Full Name
Icahn School of Medicine at Mount Sinai
Org Study Id
GCO 08-1078-0008
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Temporary Weans From LVAD Support Tolerated
Outcome Time Frame
up to 6 months
Outcome Description
Safety as assessed by number of study intervention-related adverse events
Outcome Measure
Number of Participants With Adverse Events
Outcome Time Frame
up to 6 months
Secondary Ids
Secondary Id
2U01HL088942-07
Secondary Outcomes
Outcome Description
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)
Outcome Time Frame
up to 12 months
Outcome Measure
Physiologic Assessments
Outcome Time Frame
up to 12 months
Outcome Measure
Histopathological Assessments of Myocardial Tissue
Outcome Time Frame
up to 12 months
Outcome Measure
Overall Survival
Outcome Description
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.
Outcome Time Frame
6 months and 12 months
Outcome Measure
Change in Quality of Life (QoL)
Outcome Description
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.
Outcome Time Frame
3 months and 12 months
Outcome Measure
Hopkins Verbal Learning Test
Outcome Description
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.
Outcome Time Frame
3 months and 12 months
Outcome Measure
Trailmaking Tests A and B
Outcome Description
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.
Outcome Time Frame
3 months and 12 months
Outcome Measure
MCG Complex Figures
Outcome Description
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.
Outcome Time Frame
3 months and 12 months
Outcome Measure
Digit Span
Outcome Description
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.
Outcome Time Frame
3 months and 12 months
Outcome Measure
Digit Symbol Substitution Test
Outcome Description
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.
Outcome Time Frame
3 months and 12 months
Outcome Measure
Controlled Oral Word Association
Outcome Description
Length of stay of index hospitalization
Outcome Time Frame
up to 12 months
Outcome Measure
Length of Stay
Outcome Description
Frequency and cause of readmissions
Outcome Time Frame
up to 12 months
Outcome Measure
Hospitalizations
Outcome Description
Hospital resource use
Outcome Time Frame
up to 12 months
Outcome Measure
Hospital Costs
Outcome Description
functional status, defined by the number of temporary weans from LVAD support tolerated
Outcome Time Frame
up to 12 months
Outcome Measure
Functional Status
See Also Links
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Daniel Goldstein
Investigator Email
dgoldste@montefiore.org
Investigator Phone