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Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) (PROMETHEUS)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00587990
First Posted: January 8, 2008
Last Update Posted: October 23, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University Specialized Center for Cell Based Therapy
The EMMES Corporation
Information provided by (Responsible Party):
Joshua M Hare, University of Miami
  Purpose
Heart attacks are a leading cause of death in both men and women in the United States. When a person has a heart attack, blood is unable to reach a certain area of the heart, and if the blood supply is not re-established quickly, that area of the heart can suffer permanent damage. While recovery from a heart attack can be managed through medications and lifestyle changes, these treatments can not reverse the original damage to the heart. Current research is focusing on the development of cell-based therapies using stem cells to repair organs that have been irreversibly damaged by disease. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair. This study will evaluate the safety and effectiveness of injecting MSCs into the heart to repair and restore heart function in people who have had a heart attack and who are having heart surgery for coronary artery bypass grafting (CABG).

Condition Intervention Phase
Stem Cell Transplantation Ventricular Dysfunction, Left Genetic: Lower dose mesenchymal stem cell (MSC) injection Genetic: Placebo Genetic: Higher dose MSC injection Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells (MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction (MI) Undergoing Cardiac Surgery for Coronary Artery Bypass Grafting (CABG)

Resource links provided by NLM:


Further study details as provided by Joshua M Hare, University of Miami:

Primary Outcome Measures:
  • Incidence of Serious Adverse Events (SAEs) [ Time Frame: Measured at Month 6 after surgery ]
    Incidence of serious adverse events (SAEs), defined as the 6-month post-cardiac surgery for coronary artery bypss grafting CABG SAE proportion of patients experiencing sustained ventricular arrhythmias, ectopic tissue formation, or sudden unexpected death


Secondary Outcome Measures:
  • MRI and Echocardiographic Measures of Infarct Scar Size (ISS) and Left Regional and Global Ventricular Function [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
  • Treatment Emergent Adverse Event Rates [ Time Frame: Measured over the 6-month follow-up period, at Month 12 follow-up and at Month 18 follow-up ]
  • 48-hour Ambulatory Electrocardiogram (ECG) Recordings [ Time Frame: Measured over the 6-month follow-up period, at Month 12 follow-up and at Month 18 follow-up ]
  • Hematology, Clinical Chemistry, and Urinalysis Values [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
  • Pulmonary Function - Forced Expiratory Volume in 1 Second (FEV1) Results [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
  • Cardiac Computed Tomography Measures of ISS, Left Ventricular Ejection Fraction, and End Diastolic and End Systolic Volumes [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
  • Serial Troponin and Creatine Kinase MB (CK-MB) Values [ Time Frame: Measured every 12 hours for the first 48 hours after surgery ]
  • Peak VO2 (by Treadmill Determination) and 6-minute Walk Test [ Time Frame: Measured at baseline and Months 6 and 18 follow-ups ]
  • New York Heart Association (NYHA) Functional Class [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
  • Minnesota Living With Heart Failure (MLHF) Questionnaire [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
  • Incidence of the Major Adverse Cardiac Events (MACE) Endpoint, Defined as the Composite Incidence of (1) Death, (2) Hospitalization for Heart Failure, or (3) Non-fatal Recurrent Heart Attack [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]

Enrollment: 9
Study Start Date: November 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: (1) Lower MSC dose
Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 107 cells
Genetic: Lower dose mesenchymal stem cell (MSC) injection
Participants will receive between 10 and 20 intramyocardial injections of 2 million MSCs per 0.25-0.5 cubic centimeter (cc) for a total of 2 x 107 cells. The injections will be administered following completion of CABG surgery.
Experimental: (2) Higher MSC dose
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 108 cells
Genetic: Higher dose MSC injection
Participants will receive between 10 and 20 intramyocardial injections of 20 million MSCs per 0.25-0.5 cc for a total of 2 x 108 cells. The injections will be administered following completion of CABG surgery.
Placebo Comparator: (3) Placebo
Participants will receive placebo injections
Genetic: Placebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

Detailed Description:

Participation in this study will last 18 months. Potential participants will undergo initial screening 5 to 7 weeks prior to CABG surgery. Screening will include a physical exam, blood draw, pregnancy test, questions about medical history, current medications, and alcohol or drug use, an electrocardiogram (ECG), magnetic resonance imaging (MRI) of the heart, questionnaires, an echocardiogram and a computed tomography (CT) scan. Eligible participants will then undergo two baseline visits within 6 weeks of their scheduled surgery. Baseline Visit 1 will consist of vital sign measurements, a bone marrow aspiration to obtain MSCs and a blood draw for a biomarker test. Baseline Visit 2 will include treadmill test, 6-minute walk test, pulmonary function (FEV1) study and a 48 Hour Ambulatory ECG. After the second baseline visit, participants will be assigned randomly to receive either MSCs or placebo after surgery.

On the day of surgery, once all of the bypass grafts have been placed, a high or low dose of MSCs or placebo will be injected into a damaged area of the heart that did not receive a bypass graft. After receiving the injections, participants will remain in the hospital for up to 7 days. During this stay, participants will undergo a daily blood draw, urine test, ECG, and ambulatory ECG monitoring for the first 96 hours after surgery.

Upon being discharged, participants will return for monthly visits for 6 months and for follow-up visits 12 and 18 months after surgery. These visits will repeat most initial screening and baseline tests. There will be one additional visit 14 days after surgery, which will include questions about side effects, a physical exam, and a 48-hour ambulatory ECG.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic ischemic heart failure caused by a heart attack
  • Scheduled to undergo cardiac surgery for CABG
  • Ejection fraction between 15% and 50%
  • Presence of an akinetic or dyskinetic region by standard imaging

Exclusion Criteria:

  • Glomerular filtration rate of less than 50 mL/min/1.73m2 at study entry
  • Contraindication to performance of an MRI scan
  • Bone marrow dysfunction, as evidenced by a 20% or more deviation from normal hematocrit, white blood cell count, or platelet values without another explanation
  • A coagulopathy condition not due to a reversible cause (i.e., Coumadin)
  • Known, serious radiographic contrast allergy
  • Known allergies to penicillin or streptomycin
  • Organ transplant recipient
  • Clinical history of malignancy within 5 years of study entry (e.g., 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 less than 1 year
  • On chronic therapy with immunosuppressant medication
  • Serum positive for HIV, hepatitis B, or hepatitis C
  • Female who is pregnant, nursing, or of child-bearing potential and not practicing effective birth control methods
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00587990


Locations
United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Joshua M Hare
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University Specialized Center for Cell Based Therapy
The EMMES Corporation
Investigators
Principal Investigator: Joshua M. Hare, MD University of Miami
Principal Investigator: Alan W. Heldman, MD University of Miami
Principal Investigator: Gary Gerstenblith, MD Johns Hopkins University
Principal Investigator: John V. Conte, MD Johns Hopkins University
Principal Investigator: Steven P. Schulman, MD Johns Hopkins University
  More Information

Publications:
Responsible Party: Joshua M Hare, Director, Interdisciplinary Stem Cell Institute, University of Miami
ClinicalTrials.gov Identifier: NCT00587990     History of Changes
Other Study ID Numbers: 20070598
U54HL081028 ( U.S. NIH Grant/Contract )
First Submitted: January 2, 2008
First Posted: January 8, 2008
Results First Submitted: January 30, 2015
Results First Posted: April 2, 2015
Last Update Posted: October 23, 2015
Last Verified: October 2015

Keywords provided by Joshua M Hare, University of Miami:
Chronic Ischemic Left Ventricular Dysfunction

Additional relevant MeSH terms:
Ventricular Dysfunction
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases