The Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis Pilot Study (The POSEIDON-Pilot Study)

• ClinicalTrials.gov Identifier: NCT01087996
• Recruitment Status: Completed
• First Posted: March 16, 2010
• Results First Posted: May 27, 2015
• Last Update Posted: May 27, 2015
• Sponsor: University of Miami
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); The Emmes Company, LLC
• Information provided by (Responsible Party): Joshua M Hare, University of Miami

Tracking Information

• First Submitted Date: March 15, 2010
• First Posted Date: March 16, 2010
• Results First Submitted Date: August 30, 2013
• Results First Posted Date: May 27, 2015
• Last Update Posted Date: May 27, 2015
• Study Start Date: March 2010
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 15, 2010): Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation [ Time Frame: One month post-catheterization ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 21, 2015)

• CT Infarct Size From Early Enhanced Defect: - Difference Between the Baseline and 13-month [ Time Frame: Baseline Month 13 post-catheterization ]
  Percentage change from 13-months post-catheterization to baseline.
• CT Measure of Left Ventricular Ejection Fraction [ Time Frame: Baseline Month 13 post-catheterization ]
• CT Measure of End Diastolic Volume [ Time Frame: Baseline Month 13 post-catheterization ]
• CT Measure of End Systolic Volume [ Time Frame: Baseline Month 13 post-catheterization ]
• CT Measure of Scar Size as % of LV Mass [ Time Frame: Baseline Month 13 post-catheterization ]
• Change in Distance Walked in 6-minutes From Baseline. [ Time Frame: 12-months ]
• Change in Minnesota Living With Heart Failure Total Score [ Time Frame: 12 months ]
  The Minnesota living with heart failure questionnaire uses a 6-point, zero to five, Likert scale. The total score is the sum of the 21 responses. The total score is considered the best measure of how heart failure and treatments impact a patients quality of life. The max score is 105, minimum score is 0. A lower score is considered a better quality of life.
• Change in New York Heart Association Class at 12-months [ Time Frame: 12 months ]

Original Secondary Outcome Measures (submitted: March 15, 2010)

• CT and Echocardiographic-derived measures of left ventricular function: - Difference between the baseline and 13-month infarct scar size (ISS) as determined by delayed contrast-enhanced CT [ Time Frame: Baseline and Month 6 and Month 13 post-catheterization ]
• CT and Echocardiographic-derived measures of left ventricular function: - Difference between the baseline and 13-month regional left ventricular function (at the site of autologous cell injections) as determined by CT [ Time Frame: Baseline and Month 6 and Month 13 post-catheterization ]
• CT and Echocardiographic-derived measures of left ventricular function: - Difference between the baseline and 13-month regional left ventricular wall thickening as determined by CT. [ Time Frame: Baseline and Month 6 and Month 13 post-catheterization ]
• CT and Echocardiographic-derived measures of left ventricular function: - Difference between the baseline, 6 month (echocardiogram only), and 13-month left ventricular end diastolic wall thickness as determined by CT and echocardiogram [ Time Frame: Baseline and Month 6 and Month 13 post-catheterization ]
• CT and Echocardiographic-derived measures of left ventricular function: - Difference between the baseline, 6 month (echocardiogram only), and 13-month left ventricular ejection fraction, end diastolic and end systolic volumes, as determined [ Time Frame: Baseline and Month 6 and Month 13 post-catheterization ]
• CT and Echocardiographic-derived measures of left ventricular function: - Difference between the baseline and 13-month left ventricular regional myocardial perfusion as determined by CT. [ Time Frame: Baseline and Month 6 and Month 13 post-catheterization ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis Pilot Study (The POSEIDON-Pilot Study)
• 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 Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction

Brief Summary

The technique of transplanting progenitor cells into a region of damaged myocardium, termed cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or repair necrotic, scarred, or dysfunctional myocardium. 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 cardiomyocytes, embryonic stem cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac precursors residing within the heart itself. 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.

Chronic ischemic left ventricular dysfunction resulting from heart disease 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Stem Cell Transplantation

Intervention

• Biological: Auto-hMSCs
  Biological: Autologous human mesenchymal stem cells (Auto-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10^8 (20 million) Auto-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10^8 (100 million) Auto-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10^8 (200 million) Auto-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
• Biological: Allo-hMSCs
  Biological: Allogeneic human mesenchymal stem cells (Allo-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10^8 (20 million) Allo-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10^8 (100 million) Allo-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10^8 (200 million) Allo-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.

Study Arms

• Experimental: Auto-hMSCs
  Participants will receive an injection of 20 million, 100 million or 200 million autologous human mesenchymal stem cells.
  Intervention: Biological: Auto-hMSCs
• Experimental: Allo-hMSCs
  Participants will receive an injection of 20 million, 100 million or 200 million allogeneic human mesenchymal stem cells.
  Intervention: Biological: Allo-hMSCs

Publications *

• Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW, George R, Lardo A. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012 Dec 12;308(22):2369-79. Erratum in: JAMA. 2013 Aug 21;310(7):750. George, Richard [added]; Lardo, Albert [added].
• 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). pii: e008460. doi: 10.1161/JAHA.117.008460.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 21, 2015): 31
• Original Estimated Enrollment (submitted: March 15, 2010): 30
• Actual Study Completion Date: October 2012
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of chronic ischemic left ventricular dysfunction secondary to MI.
• Be a candidate for cardiac catheterization.
• Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction.
• Ejection fraction between 20% and 50%.
• Able to perform a metabolic stress test.

Exclusion Criteria:

• Baseline glomerular filtration rate <50 ml/min/1.73m2.
• Presence of a mechanical aortic valve or heart constrictive device.
• Documented presence of aortic stenosis (aortic stenosis graded as ≥+2 equivalent to an orifice area of 1.5cm2 or less).
• Documented presence of moderate to severe aortic insufficiency (echocardio- graphic assessment of aortic insufficiency graded as ≥+2).
• Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥20 consecutive beats or complete heart block) or QTc interval >550 ms on screening ECG. In addition; patients with sustained or a short run of ventricular tachycardia on ECG or 48 hour Ambulatory ECG during the screening period will be removed from the protocol.
• Documented unstable angina.
• AICD firing in the past 60 days prior to the procedure.
• Be eligible for or require coronary artery revascularization.
• 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 hepatitis C.
• Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01087996
• Other Study ID Numbers: 20090352; R01HL110737 ( U.S. NIH Grant/Contract ); R01HL107110 ( U.S. NIH Grant/Contract ); R01HL084275 ( U.S. NIH Grant/Contract ); P20HL101443 ( U.S. NIH Grant/Contract ); R01HL094849 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Joshua M Hare, University of Miami
• Study Sponsor: University of Miami

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• The Emmes Company, LLC

Investigators

• Principal Investigator: Joshua M Hare, MD; University of Miami

• PRS Account: University of Miami
• Verification Date: May 2015