Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) (PROMETHEUS)
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|ClinicalTrials.gov Identifier: NCT00587990|
Recruitment Status : Completed
First Posted : January 8, 2008
Results First Posted : April 2, 2015
Last Update Posted : December 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Stem Cell Transplantation Ventricular Dysfunction, Left||Biological: Lower dose mesenchymal stem cell (MSC) injection Genetic: Placebo Biological: Higher dose MSC injection||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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)|
|Study Start Date :||November 2007|
|Actual Primary Completion Date :||June 2011|
|Actual Study Completion Date :||June 2011|
Experimental: Lower dose mesenchymal stem cell (MSC) injection
Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 10^7 cells
Biological: 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 10^7 cells. The injections will be administered following completion of CABG surgery.
Experimental: Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
Biological: 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 10^8 cells. The injections will be administered following completion of CABG surgery.
Placebo Comparator: (3) Placebo
Participants will receive placebo injections
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).
- 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
- 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 ]
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
|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|
|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|