Clinical trial NCT00587990: Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Stem Cell Transplantation
Ventricular Dysfunction, Left
Keywords: Chronic Ischemic Left Ventricular Dysfunction
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Johns Hopkins University Specialized Center for Cell Based Therapy
name: The Emmes Company, LLC
First posted: 2008-01-08
Enrollment: 9
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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 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

Primary outcomes:
measure: Number of Patients With Serious Adverse Events
timeFrame: 12 Months
Secondary outcomes:
measure: Change in Infarct Scar Size (ISS) Over 18 Month Period
timeFrame: Baseline, 6 Months, 18 Months
measure: Left Ventricular Function (LVF) in Region of MSC Injection
timeFrame: Assessed at Baseline and 18 Months
measure: Regional Left Ventricular Wall Thickening
timeFrame: Assessed at Baseline and 18 months
measure: Left Ventricular End Diastolic Wall Thickness
timeFrame: Assessed at Baseline and 18 months
measure: Change in Left Ventricular End Diastolic and Systolic Volume
timeFrame: Baseline, 6 Months, 18 Months
measure: Change in Left Ventricular Ejection Fraction
timeFrame: Baseline to 6 Months, Baseline to 18 Months
measure: Change in Peak Volume Oxygen
timeFrame: Baseline, 6 Months, 18 Months
measure: Change in Six Minute Walk Test
timeFrame: Baseline, 6 Months, 18 Months
measure: Change in NYHA Functional Class
timeFrame: Baseline to 6 Months, 6 months to 18 Months
measure: Minnesota Living With Heart Failure Questionnaire Scores
timeFrame: Assessed at 6 Months and 18 Months
measure: Incidence of Major Adverse Cardiac Events (MACE)
timeFrame: 18 Months
measure: Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings
timeFrame: Assessed at 6 Months, 12 Months, and 18 Months
measure: Change in Pulmonary Function
timeFrame: Baseline, 6 Months, 12 Months, 18 Months
measure: Serial Troponin Values (ng/mL)
timeFrame: Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG
measure: Creatinine Kinase - Muscle/Brain (MB) (ng/mL)
timeFrame: Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG
measure: Number of Clinically Significant Laboratory Values
timeFrame: 18 Months
measure: Rate of Treatment Emergent Adverse Events
timeFrame: Assessed at 6 Months, 12 Months, and 18 Months
measure: Number of Abnormal Echocardiogram Readings 2 Days Post CABG.
timeFrame: Day 2
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: University of Miami
name: Joshua M. Hare, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Gary Gerstenblith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: John V. Conte, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Steven P. Schulman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karantalis V, DiFede DL, Gerstenblith G, Pham S, Symes J, Zambrano JP, Fishman J, Pattany P, McNiece I, Conte J, Schulman S, Wu K, Shah A, Breton E, Davis-Sproul J, Schwarz R, Feigenbaum G, Mushtaq M, Suncion VY, Lardo AC, Borrello I, Mendizabal A, Karas TZ, Byrnes J, Lowery M, Heldman AW, Hare JM. Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ Res. 2014 Apr 11;114(8):1302-10. doi: 10.1161/CIRCRESAHA.114.303180. Epub 2014 Feb 24.