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

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Collaborator:	Johns Hopkins University Specialized Center for Cell Based Therapy
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00587990

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 I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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:

MedlinePlus related topics: Coronary Artery Bypass Surgery Heart Attack Heart Surgery

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Incidence of serious adverse events (SAEs), defined as the 6-month post-CABG surgery SAE proportion of patients experiencing sustained ventricular arrhythmias, ectopic tissue formation, or sudden unexpected death [ Time Frame: Measured at Month 6 after surgery ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
Hematology, clinical chemistry, and urinalysis values [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Serial troponin and creatine kinase MB (CK-MB) values [ Time Frame: Measured every 12 hours for the first 48 hours after surgery ] [ Designated as safety issue: Yes ]
Peak VO2 (by treadmill determination) and 6-minute walk test [ Time Frame: Measured at baseline and Months 6 and 18 follow-ups ] [ Designated as safety issue: No ]
New York Heart Association (NYHA) functional class [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
Minnesota Living with Heart Failure (MLHF) questionnaire [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	November 2007
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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 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 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

Ages Eligible for Study:	21 Years to 80 Years
Genders Eligible for Study:	Both
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

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

National Heart, Lung, and Blood Institute (NHLBI)

Johns Hopkins University Specialized Center for Cell Based Therapy

Investigators

Principal Investigator:	Joshua M. Hare, MD	University of Miami Miller School of Medicine
Principal Investigator:	Alan W. Heldman, MD	University of Miami Miller School of Medicine
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

No publications provided

Responsible Party:	Joshua M. Hare, MD, University of Miami
ClinicalTrials.gov Identifier:	NCT00587990 History of Changes
Other Study ID Numbers:	362, U54 HL081028
Study First Received:	January 2, 2008
Last Updated:	April 21, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Chronic Ischemic Left Ventricular Dysfunction

Additional relevant MeSH terms:

Myocardial Infarction
Ventricular Dysfunction, Left
Ventricular Dysfunction
Myocardial Ischemia

Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on February 09, 2012