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).
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
9
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.
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).
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.
University of Miami Miller School of Medicine
Miami, Florida, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Number of Patients With Serious Adverse Events
Six-month post-CABG surgery serious adverse event (SAE) proportion of patients experiencing a composite of sustained ventricular arrhythmias, (lasting longer than 15 seconds), with hemodynamic compromise, sudden unexpected death at six months, ectopic tissue formation at 12 months by chest/abdomen/pelvis CT exam.
Time frame: 12 Months
Change in Infarct Scar Size (ISS) Over 18 Month Period
Change in infarct scar size (ISS) between baseline and 6-month and 18 month visits as determined by delayed contrast-enhanced MRI.
Time frame: Baseline, 6 Months, 18 Months
Left Ventricular Function (LVF) in Region of MSC Injection
The Left Ventricular Function differences in the region of MSC injection were evaluated. LVF is evaluated via ECHO as the percentage of ejected blood.
Time frame: Assessed at Baseline and 18 Months
Regional Left Ventricular Wall Thickening
Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI.
Time frame: Assessed at Baseline and 18 months
Left Ventricular End Diastolic Wall Thickness
Difference between the baseline and 18 month left ventricular end diastolic wall thickness as determined by MRI and echocardiogram.
Time frame: Assessed at Baseline and 18 months
Change in Left Ventricular End Diastolic and Systolic Volume
Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram.
Time frame: Baseline, 6 Months, 18 Months
Change in Left Ventricular Ejection Fraction
Change between baseline to 6-month and 18-month left ventricular ejection fraction (LVEF) as determined by MRI and echocardiogram.
Time frame: Baseline to 6 Months, Baseline to 18 Months
Change in Peak Volume Oxygen
Change in Peak VO2 as determined by treadmill test (mL/mg/min) from Baseline to 6 and from baseline to 18 months
Time frame: Baseline, 6 Months, 18 Months
Change in Six Minute Walk Test
Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months
Time frame: Baseline, 6 Months, 18 Months
Change in NYHA Functional Class
Change in New York Heart Association (NYHA) Functional Classification based on patient's self reported activity level. Worsened: documented increase in limitations of physical activity as self-described by subject Improved: documented decrease in limitations of physical activity as self-described by subject Unchanged: no documented change in limitations of physical activity as self-described by subject
Time frame: Baseline to 6 Months, 6 months to 18 Months
Minnesota Living With Heart Failure Questionnaire Scores
Minnesota Living with Heart Failure (MLHF) questionnaire has a total score from 0 to 105. A higher score indicates that participants heart failure is preventing them from living their lives measured at two time points.
Time frame: Assessed at 6 Months and 18 Months
Incidence of Major Adverse Cardiac Events (MACE)
Incidence of Major Adverse Cardiac Events (MACE). A composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent Ml.
Time frame: 18 Months
Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings
Ambulatory ECG monitoring is the most widely employed technology for the evaluation of a patient with symptoms suggestive of cardiac arrhythmia or conduction abnormality. When the patient returns for follow up the 48- Hour Ambulatory monitor provides the data to the site staff to detect any abnormal recordings based upon standard ECG protocol.
Time frame: Assessed at 6 Months, 12 Months, and 18 Months
Change in Pulmonary Function
Change in Pulmonary Function from Baseline to 6 month, Baseline to 12 month, and Baseline to 18 month visits as measured by forced expiratory volume in 1 second (FEV1)
Time frame: Baseline, 6 Months, 12 Months, 18 Months
Serial Troponin Values (ng/mL)
Serial Troponin Values (ng/mL) Values from Baseline to 48 Hours Post CABG
Time frame: Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG
Creatinine Kinase - Muscle/Brain (MB) (ng/mL)
Creatinine Kinase MB (ng/mL) Values every 12 hours from Baseline to 48 Hours Post CABG
Time frame: Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG
Number of Clinically Significant Laboratory Values
Clinically significant laboratory values are first determined via standard laboratory normal values from a CAP and CLIA certified Laboratory and then assessed by investigator based on specific patient conditions and disease state.
Time frame: 18 Months
Rate of Treatment Emergent Adverse Events
Rate of Treatment Emergent Adverse Events Post Coronary Artery Bypass Graft (CABG) at 6 Months, 12 Months, and 18 Months
Time frame: Assessed at 6 Months, 12 Months, and 18 Months
Number of Abnormal Echocardiogram Readings 2 Days Post CABG.
The number of abnormal Echocardiogram readings 2 Days Post CABG will be documented based on transthoracic Echocardiographic standards. However, although Echocardiograms 2 days post CABG operation may show abnormalities which is standard in this population, this testing is instrumental because it measures End- diastolic wall thickness and Left ventricular volumes at end-diastole and end-systole.
Time frame: Day 2
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