PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis in Dilated CardioMyopathy (The POSEIDON-DCM Study)
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 95 |
| Updated: | 2/17/2018 |
| Start Date: | May 19, 2011 |
| End Date: | August 28, 2017 |
A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Non-ischemic Dilated Cardiomyopathy.
The technique of transplanting progenitor cells into a region of damaged myocardium, termed
cellular cardiomyoplasty1, is a potentially new therapeutic modality designed to replace or
repair necrotic, scarred, or dysfunctional myocardium2-4. Ideally, graft cells should be
readily available, easy to culture to ensure adequate quantities for transplantation, and
able to survive in host myocardium; often a hostile environment of limited blood supply and
immunorejection. Whether effective cellular regenerative strategies require that administered
cells differentiate into adult cardiomyocytes and couple electromechanically with the
surrounding myocardium is increasingly controversial and recent evidence suggests that this
may not be required for effective cardiac repair. Most importantly, transplantation of graft
cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a
number of candidate cells have been transplanted in experimental models, including fetal and
neonatal cardiomyocytes5, embryonic stem cell-derived myocytes6, 7, tissue engineered
contractile grafts8, skeletal myoblasts9, several cell types derived from adult bone
marrow10-15, and cardiac precursors residing within the heart itself16. There has been
substantial clinical development in the use of whole bone marrow and skeletal myoblast
preparations in studies enrolling both post-infarction patients, and patients with chronic
ischemic left ventricular dysfunction and heart failure. The effects of bone-marrow derived
mesenchymal stem cells (MSCs) have also been studied clinically.
Currently, bone marrow or bone marrow-derived cells represent highly promising modality for
cardiac repair. The totality of evidence from trials investigating autologous whole bone
marrow infusions into patients following myocardial infarction supports the safety of this
approach. In terms of efficacy, increases in ejection fraction are reported in the majority
of the trials.
Non-ischemic dilated cardiomyopathy is a common and problematic condition; definitive therapy
in the form of heart transplantation is available to only a tiny minority of eligible
patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for
acute MI, but represents a potentially important alternative for this disease.
cellular cardiomyoplasty1, is a potentially new therapeutic modality designed to replace or
repair necrotic, scarred, or dysfunctional myocardium2-4. Ideally, graft cells should be
readily available, easy to culture to ensure adequate quantities for transplantation, and
able to survive in host myocardium; often a hostile environment of limited blood supply and
immunorejection. Whether effective cellular regenerative strategies require that administered
cells differentiate into adult cardiomyocytes and couple electromechanically with the
surrounding myocardium is increasingly controversial and recent evidence suggests that this
may not be required for effective cardiac repair. Most importantly, transplantation of graft
cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a
number of candidate cells have been transplanted in experimental models, including fetal and
neonatal cardiomyocytes5, embryonic stem cell-derived myocytes6, 7, tissue engineered
contractile grafts8, skeletal myoblasts9, several cell types derived from adult bone
marrow10-15, and cardiac precursors residing within the heart itself16. There has been
substantial clinical development in the use of whole bone marrow and skeletal myoblast
preparations in studies enrolling both post-infarction patients, and patients with chronic
ischemic left ventricular dysfunction and heart failure. The effects of bone-marrow derived
mesenchymal stem cells (MSCs) have also been studied clinically.
Currently, bone marrow or bone marrow-derived cells represent highly promising modality for
cardiac repair. The totality of evidence from trials investigating autologous whole bone
marrow infusions into patients following myocardial infarction supports the safety of this
approach. In terms of efficacy, increases in ejection fraction are reported in the majority
of the trials.
Non-ischemic dilated cardiomyopathy is a common and problematic condition; definitive therapy
in the form of heart transplantation is available to only a tiny minority of eligible
patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for
acute MI, but represents a potentially important alternative for this disease.
This is a Pilot Study, intended as a safety assessment prior to a full comparator study. In
this Pilot Study, cells administered via the Biosense Webster MyoStar NOGA injection catheter
system will be tested in 36 patients in two groups:
Group 1 (18 patients) Eighteen (18) patients will be treated with Auto-hMSCs: 20 million
cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 X 108
(100 million) Auto-hMSCs.
Group 2 (18 patients) Eighteen (18) patients will be treated with Allo-hMSCs: 20 million
cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 X 108
(100 million) Auto-hMSCs.
The first three (3) patients in each group (Group 1 and Group 2) will not be treated less
than 5 days apart and will each undergo full evaluation for 5 days to demonstrate there is no
evidence of a procedure induced myocardial infarction or myocardial perforation prior to
proceeding with the treatment of further patients.
Patients will be randomized in a 1:1 ratio to one of the two groups.
Treatment Strategies: Autologous hMSCs vs. Allogeneic hMSCs. The Study Team will record and
maintain a detailed record of injection locations.
If a patient is randomized to Groups 1 (Auto-hMSCs) and the Auto-hMSCs do not expand to the
required dose of 1 X 108 cells, each injection will contain the maximum number of cells
available.
The injections will be administered transendocardially during cardiac catheterization using
the Biosense Webster MyoStar NOGA Catheter System.
For patients randomized to Group 1(Auto-hMSCs); the cells will be derived from a sample of
the patient's bone marrow (obtained by iliac crest aspiration) approximately 4-6 weeks prior
to cardiac catheterization. For patients randomized to Group 2 (Allo- hMSCs), the cells will
be supplied from an allogeneic human mesenchymal stem cell source manufactured by the
University of Miami. The Allo-hMSCs for patients in group 2 will be administered after all
baseline assessments are completed with an expected range of 2 - 4 weeks post-randomization.
Following cardiac catheterization and cell injections, patients will be hospitalized for a
minimum of 2 days then followed at 2 weeks post-catheterization, and at month 2, 3, 6, and 12
to complete all safety and efficacy assessments.
this Pilot Study, cells administered via the Biosense Webster MyoStar NOGA injection catheter
system will be tested in 36 patients in two groups:
Group 1 (18 patients) Eighteen (18) patients will be treated with Auto-hMSCs: 20 million
cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 X 108
(100 million) Auto-hMSCs.
Group 2 (18 patients) Eighteen (18) patients will be treated with Allo-hMSCs: 20 million
cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1 X 108
(100 million) Auto-hMSCs.
The first three (3) patients in each group (Group 1 and Group 2) will not be treated less
than 5 days apart and will each undergo full evaluation for 5 days to demonstrate there is no
evidence of a procedure induced myocardial infarction or myocardial perforation prior to
proceeding with the treatment of further patients.
Patients will be randomized in a 1:1 ratio to one of the two groups.
Treatment Strategies: Autologous hMSCs vs. Allogeneic hMSCs. The Study Team will record and
maintain a detailed record of injection locations.
If a patient is randomized to Groups 1 (Auto-hMSCs) and the Auto-hMSCs do not expand to the
required dose of 1 X 108 cells, each injection will contain the maximum number of cells
available.
The injections will be administered transendocardially during cardiac catheterization using
the Biosense Webster MyoStar NOGA Catheter System.
For patients randomized to Group 1(Auto-hMSCs); the cells will be derived from a sample of
the patient's bone marrow (obtained by iliac crest aspiration) approximately 4-6 weeks prior
to cardiac catheterization. For patients randomized to Group 2 (Allo- hMSCs), the cells will
be supplied from an allogeneic human mesenchymal stem cell source manufactured by the
University of Miami. The Allo-hMSCs for patients in group 2 will be administered after all
baseline assessments are completed with an expected range of 2 - 4 weeks post-randomization.
Following cardiac catheterization and cell injections, patients will be hospitalized for a
minimum of 2 days then followed at 2 weeks post-catheterization, and at month 2, 3, 6, and 12
to complete all safety and efficacy assessments.
Major Inclusion Criteria:
- Be ≥ 18 and < 95 years of age.
- Provide written informed consent.
- Diagnosis of nonischemic dilated cardiomyopathy.
- Be a candidate for cardiac catheterization within 5 to 10 weeks of screening.
- Been treated with appropriate maximal medical therapy for heart failure.
- Ejection fraction below 40% and either a left ventricular end diastolic diameter
(LVEDD) > 5.9cm in male subjects, an LVEDD of > 5.6cm in female subjects or left
ventricular end diastolic volume index > 125 mL/m2
- Be able to undergo an MRI or CT.
Major Exclusion Criteria:
- Baseline glomerular filtration rate equal or < 45 ml/min/1.73m2.
- Be eligible for or require standard-of-care surgical or percutaneous intervention for
the treatment of nonischemic dilated cardiomyopathy.
- Presence of a prosthetic aortic valve or heart constrictive device.
- Presence of a prosthetic mitral valve.
- Previous myocardial infarction (MI) as documented by a clinical history that will
include an elevation of cardiac enzymes and/or ECG changes consistent with MI.
- Diagnosis of nonischemic dilated cardiomyopathy due to valvular dysfunction, mitral
regurgitation, tachycardia, or myocarditis.
- Previous treatment for post-infarction left ventricular dysfunction including PCI and
thrombolytic therapy.
- Documented presence of a known LV thrombus, aortic dissection, or aortic aneurysm.
- Documented presence of epicardial stenosis of 70% or greater in one or more major
epicardial coronary arteries.
- Documented presence of aortic stenosis (aortic stenosis graded as 1.5cm2 or less).
- Documented presence of moderate to severe aortic insufficiency (echocardiographic
assessment of aortic insufficiency graded as ≥+2).
- Evidence of a life-threatening arrhythmia in the absence of a defibrillator
(nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete second or
third degree heart block in the absence of a functioning pacemaker) or QTc interval >
550 ms on screening ECG.
- AICD firing in the past 30 days prior to the procedure
- Be eligible for or require coronary artery revascularization.
- Diabetic with poorly controlled blood glucose levels and/or evidence of proliferative
retinopathy.
- Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell <
2,500/ul or platelet values < 100,000/ul without another explanation.
- Have liver dysfunction, as evidenced by enzymes (ALT and AST) greater than three times
the ULN.
- Have a coagulopathy condition = (INR > 1.3) not due to a reversible cause.
- Known, serious radiographic contrast allergy.
- Known allergies to penicillin or streptomycin.
- Organ transplant recipient.
- Have a history of organ or cell transplant rejection
- Clinical history of malignancy within 5 years (i.e., patients with prior malignancy
must be disease free for 5 years), except curatively-treated basal cell carcinoma,
squamous cell carcinoma, or cervical carcinoma.
- Non-cardiac condition that limits lifespan to < 1 year.
- On chronic therapy with immunosuppressant medication.
- Serum positive for HIV, hepatitis BsAg, or viremic hepatitis C.
- Female patient who is pregnant, nursing, or of child-bearing potential and not using
effective birth control.
- Have a history of drug or alcohol abuse within the past 24 months.
- Be currently participating (or participated within the previous 30 days) in an
investigational therapeutic or device trial.
We found this trial at
1
site
Click here to add this to my saved trials
