Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) (PROMETHEUS)
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| ClinicalTrials.gov Identifier: NCT00587990 |
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Recruitment Status :
Terminated
(Difficulty in recruitment.)
First Posted : January 8, 2008
Results First Posted : April 2, 2015
Last Update Posted : September 10, 2019
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| 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 |
| 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) |
| Study Start Date : | November 2007 |
| Actual Primary Completion Date : | June 2011 |
| Actual Study Completion Date : | June 2011 |
| Arm | Intervention/treatment |
|---|---|
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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
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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. |
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Experimental: Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
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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. |
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Placebo Comparator: (3) Placebo
Participants will receive placebo injections
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Genetic: Placebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA). |
- Number of Patients With Serious Adverse Events [ Time Frame: 12 Months ]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.
- Change in Infarct Scar Size (ISS) Over 18 Month Period [ Time Frame: Baseline, 6 Months, 18 Months ]Change in infarct scar size (ISS) between baseline and 6-month and 18 month visits as determined by delayed contrast-enhanced MRI.
- Left Ventricular Function (LVF) in Region of MSC Injection [ Time Frame: Assessed at Baseline and 18 Months ]The Left Ventricular Function differences in the region of MSC injection were evaluated. LVF is evaluated via ECHO as the percentage of ejected blood.
- Regional Left Ventricular Wall Thickening [ Time Frame: Assessed at Baseline and 18 months ]Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI.
- Left Ventricular End Diastolic Wall Thickness [ Time Frame: Assessed at Baseline and 18 months ]Difference between the baseline and 18 month left ventricular end diastolic wall thickness as determined by MRI and echocardiogram.
- Change in Left Ventricular End Diastolic and Systolic Volume [ Time Frame: Baseline, 6 Months, 18 Months ]Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram.
- Change in Left Ventricular Ejection Fraction [ Time Frame: Baseline to 6 Months, Baseline to 18 Months ]Change between baseline to 6-month and 18-month left ventricular ejection fraction (LVEF) as determined by MRI and echocardiogram.
- Change in Peak Volume Oxygen [ Time Frame: Baseline, 6 Months, 18 Months ]Change in Peak VO2 as determined by treadmill test (mL/mg/min) from Baseline to 6 and from baseline to 18 months
- Change in Six Minute Walk Test [ Time Frame: Baseline, 6 Months, 18 Months ]Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months
- Change in NYHA Functional Class [ Time Frame: Baseline to 6 Months, 6 months to 18 Months ]
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
- Minnesota Living With Heart Failure Questionnaire Scores [ Time Frame: Assessed at 6 Months and 18 Months ]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.
- Incidence of Major Adverse Cardiac Events (MACE) [ Time Frame: 18 Months ]Incidence of Major Adverse Cardiac Events (MACE). A composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent Ml.
- Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings [ Time Frame: Assessed at 6 Months, 12 Months, and 18 Months ]
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.
- Change in Pulmonary Function [ Time Frame: Baseline, 6 Months, 12 Months, 18 Months ]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)
- Serial Troponin Values (ng/mL) [ Time Frame: Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG ]Serial Troponin Values (ng/mL) Values from Baseline to 48 Hours Post CABG
- Creatinine Kinase - Muscle/Brain (MB) (ng/mL) [ Time Frame: Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG ]Creatinine Kinase MB (ng/mL) Values every 12 hours from Baseline to 48 Hours Post CABG
- Number of Clinically Significant Laboratory Values [ Time Frame: 18 Months ]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.
- Rate of Treatment Emergent Adverse Events [ Time Frame: Assessed at 6 Months, 12 Months, and 18 Months ]Rate of Treatment Emergent Adverse Events Post Coronary Artery Bypass Graft (CABG) at 6 Months, 12 Months, and 18 Months
- Number of Abnormal Echocardiogram Readings 2 Days Post CABG. [ Time Frame: Day 2 ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 21 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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: | Gary Gerstenblith, MD | Johns Hopkins University | |
| Principal Investigator: | John V. Conte, MD | Johns Hopkins University | |
| Principal Investigator: | Steven P. Schulman, MD | Johns Hopkins University |
| Responsible Party: | Joshua M Hare, Director, Interdisciplinary Stem Cell Institute, University of Miami |
| ClinicalTrials.gov Identifier: | NCT00587990 |
| Other Study ID Numbers: |
20070598 U54HL081028 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 8, 2008 Key Record Dates |
| Results First Posted: | April 2, 2015 |
| Last Update Posted: | September 10, 2019 |
| Last Verified: | August 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Chronic Ischemic Left Ventricular Dysfunction |
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Ventricular Dysfunction Ventricular Dysfunction, Left Heart Diseases Cardiovascular Diseases |