PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis in Dilated CardioMyopathy (The POSEIDON-DCM Study) (PoseidonDCM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Miami
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Joshua M Hare, University of Miami
ClinicalTrials.gov Identifier:
NCT01392625
First received: June 29, 2011
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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.

Nonischemic 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.


Condition Intervention Phase
Non-ischemic Dilated Cardiomyopathy
Procedure: Transendocardial injection
Biological: Autologous hMSCs
Biological: Allogeneic hMSCs
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 Nonischemic Dilated Cardiomyopathy.

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Incidence of any treatment-emergent serious adverse events (TE-SAEs) [ Time Frame: One month post-catheterization ] [ Designated as safety issue: Yes ]
    Incidence of TE-SAEs is defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise).


Secondary Outcome Measures:
  • Measurement of Changes in Regional Left Ventricular function [ Time Frame: Baseline, 6 month and 12 month ] [ Designated as safety issue: No ]
    Measurement of regional left ventricular function, wall thickening, end diastolic and end systolic volume,including tissue perfusion measured by MRI, and or CT, and echocardiogram. Other measurements include: Peak VO2 (by treadmill determination),Six-minute walk test,NYHA functional class, Minnesota Living with Heart Failure (MLHF) Questionnaire, Incidence of the Major Adverse Cardiac Events (MACE) endpoint, defined as the composite incidence of (1) death, (2) hospitalization for worsening heart failure, (3) non-fatal recurrent MI, or (4) angina requiring hospitalization.


Estimated Enrollment: 36
Study Start Date: June 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Autologous hMSCs
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.
Procedure: Transendocardial injection

Cells will be 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.

Other Name: Biosense Webster MyoStar NOGA Injection Catheter System.
Biological: Autologous hMSCs
Active Comparator: Allogeneic ahMSC
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.
Procedure: Transendocardial injection

Cells will be 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.

Other Name: Biosense Webster MyoStar NOGA Injection Catheter System.
Biological: Allogeneic hMSCs

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   21 Years to 94 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Major Inclusion Criteria:

  • 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 or left ventricular end diastolic volume index > 125 mL/m2

Major Exclusion Criteria:

  • Baseline glomerular filtration rate < 50 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392625

Contacts
Contact: Joshua M Hare, MD 305-243-5579 jhare@med.miami.edu
Contact: Darcy L Velazquez, RN,BSN 305-243-9106 dvelazqu@med.miami.edu

Locations
United States, Florida
University of Miami School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Joshua M Hare, MD    305-243-5579    jhare@med.miami.edu   
Contact: Darcy L Velazquez, RN, BSN    305-243-9106    dvelazqu@med.miami.edu   
Principal Investigator: Joshua M Hare, MD         
Sponsors and Collaborators
Joshua M Hare
Investigators
Principal Investigator: Joshua M Hare, MD University of Miami
  More Information

Additional Information:
Publications:
Responsible Party: Joshua M Hare, Sponsor- Investigator; Director of ISCI, Chief Science Officer, University of Miami
ClinicalTrials.gov Identifier: NCT01392625     History of Changes
Other Study ID Numbers: 20100968, 1R01HL110737-01
Study First Received: June 29, 2011
Last Updated: August 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Non ischemic dilated cardiomyopathy
Dilated cardiomyopathy
Heart failure
Cardiac Stem Cell Transplantation
Stem Cells

Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Cardiomegaly

ClinicalTrials.gov processed this record on September 22, 2014