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

NCT01392625 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 201009681R01HL110737-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-ischemic Dilated Cardiomyopathy

Keywords

Non ischemic dilated cardiomyopathy; Dilated cardiomyopathy; Heart failure; Cardiac Stem Cell Transplantation; Stem Cells

Outcome Measures

Primary Outcomes (1)

• Incidence of Any Treatment-emergent Serious Adverse Events (TE-SAEs)

  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), or any other potential late effects detected and corroborated by clinical presentation, laboratory investigations, image analysis and when necessary with biopsy from suspected target sites in the body.

  One month post-catheterization

Secondary Outcomes (5)

• Measurement of Changes in Peak VO2

  Baseline, 6 month and 12 month

• Measurement of Changes in 6 Minute Walk

  Baseline, 6 month and 12 month

• Measurement of Changes in Global Ejection Fraction

  Baseline, 6 month and 12 month

• Measurement of Changes in New York Heart Association (NYHA)

  Baseline, 6 month and 12 month

• Measurement of Changes in Minnesota Living With Heart Failure (MLHF) Questionnaire

  Baseline, 6 month and 12 month

Study Arms (2)

Autologous hMSCs

ACTIVE COMPARATOR

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.

Biological: Autologous hMSCs

Allogeneic hMSCs

ACTIVE COMPARATOR

Group 2 (18 patients) Eighteen (18) patients will be treated with allogeneic hMSCs (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.

Biological: Allogeneic hMSCs

Interventions

Autologous hMSCs BIOLOGICAL

Cells will be administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested in 18 patients via transendocardial injection: 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.

Also known as: Biosense Webster MyoStar NOGA Injection Catheter System.

Autologous hMSCs

Allogeneic hMSCs BIOLOGICAL

Cells will be administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested in 18 patients via transendocardial injection: 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.

Also known as: Biosense Webster MyoStar NOGA Injection Catheter System.

Allogeneic hMSCs

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joshua M Hare: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (6)

• Williams AR, Trachtenberg B, Velazquez DL, McNiece I, Altman P, Rouy D, Mendizabal AM, Pattany PM, Lopera GA, Fishman J, Zambrano JP, Heldman AW, Hare JM. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circ Res. 2011 Apr 1;108(7):792-6. doi: 10.1161/CIRCRESAHA.111.242610. Epub 2011 Mar 17.

  PMID: 21415390 BACKGROUND

• Trachtenberg B, Velazquez DL, Williams AR, McNiece I, Fishman J, Nguyen K, Rouy D, Altman P, Schwarz R, Mendizabal A, Oskouei B, Byrnes J, Soto V, Tracy M, Zambrano JP, Heldman AW, Hare JM. Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy. Am Heart J. 2011 Mar;161(3):487-93. doi: 10.1016/j.ahj.2010.11.024.

  PMID: 21392602 BACKGROUND

• Hare JM, DiFede DL, Rieger AC, Florea V, Landin AM, El-Khorazaty J, Khan A, Mushtaq M, Lowery MH, Byrnes JJ, Hendel RC, Cohen MG, Alfonso CE, Valasaki K, Pujol MV, Golpanian S, Ghersin E, Fishman JE, Pattany P, Gomes SA, Delgado C, Miki R, Abuzeid F, Vidro-Casiano M, Premer C, Medina A, Porras V, Hatzistergos KE, Anderson E, Mendizabal A, Mitrani R, Heldman AW. Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017 Feb 7;69(5):526-537. doi: 10.1016/j.jacc.2016.11.009. Epub 2016 Nov 14.

  PMID: 27856208 BACKGROUND

• Premer C, Wanschel A, Porras V, Balkan W, Legendre-Hyldig T, Saltzman RG, Dong C, Schulman IH, Hare JM. Mesenchymal Stem Cell Secretion of SDF-1alpha Modulates Endothelial Function in Dilated Cardiomyopathy. Front Physiol. 2019 Sep 24;10:1182. doi: 10.3389/fphys.2019.01182. eCollection 2019.

  PMID: 31616309 DERIVED

• Tompkins BA, Rieger AC, Florea V, Banerjee MN, Natsumeda M, Nigh ED, Landin AM, Rodriguez GM, Hatzistergos KE, Schulman IH, Hare JM. Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy. J Am Heart Assoc. 2018 Jul 12;7(14):e008460. doi: 10.1161/JAHA.117.008460.

  PMID: 30005555 DERIVED

• Mushtaq M, DiFede DL, Golpanian S, Khan A, Gomes SA, Mendizabal A, Heldman AW, Hare JM. Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy. J Cardiovasc Transl Res. 2014 Dec;7(9):769-80. doi: 10.1007/s12265-014-9594-0. Epub 2014 Oct 30.

  PMID: 25354998 DERIVED

Related Links

• Interdisciplinary Stem Cell Institute University of Miami

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Heart Failure

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Joshua M. Hare, MD
• Organization: ISCI / University of Miami Miller School of Medicine

JHare@med.miami.edu

305-243-5579

Study Officials

• Joshua M Hare, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor- Investigator; Director of ISCI, Chief Science Officer

Study Record Dates

• First Submitted: June 29, 2011
• First Posted: July 12, 2011
• Study Start: May 19, 2011
• Primary Completion: August 28, 2016
• Study Completion: August 28, 2017
• Last Updated: February 15, 2018
• Results First Posted: February 15, 2018

Record last verified: 2018-01

Locations

US (1)