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

Stem Cell Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01087996
• Other study ID #: 20090352
• Secondary ID: R01HL110737R01HL
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 15, 2010
• Last updated: May 21, 2015
• Start date: March 2010
• Est. completion date: October 2012

Study information

• Verified date: May 2015
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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.
• 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.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Miami Miller School of Medicine	Miami	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Miami	National Heart, Lung, and Blood Institute (NHLBI), The EMMES Corporation

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, D — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		One month post-catheterization	Yes
Secondary	CT Infarct Size From Early Enhanced Defect: - Difference Between the Baseline and 13-month	Percentage change from 13-months post-catheterization to baseline.	Baseline Month 13 post-catheterization	No
Secondary	CT Measure of Left Ventricular Ejection Fraction		Baseline Month 13 post-catheterization	No
Secondary	CT Measure of End Diastolic Volume		Baseline Month 13 post-catheterization	No
Secondary	CT Measure of End Systolic Volume		Baseline Month 13 post-catheterization	No
Secondary	CT Measure of Scar Size as % of LV Mass		Baseline Month 13 post-catheterization	No
Secondary	Change in Distance Walked in 6-minutes From Baseline.		12-months	No
Secondary	Change in Minnesota Living With Heart Failure Total Score	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.	12 months	No
Secondary	Change in New York Heart Association Class at 12-months		12 months	No