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

NCT ID: NCT00587990

Last Updated: 2019-09-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2011-06-30

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.

Conditions

Stem Cell Transplantation; Ventricular Dysfunction, Left

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Lower dose mesenchymal stem cell (MSC) injection

Intervention Type: BIOLOGICAL

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.

Higher dose MSC injection

Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10\^8 cells

Group Type: EXPERIMENTAL

Higher dose MSC injection

Intervention Type: BIOLOGICAL

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.

(3) Placebo

Participants will receive placebo injections

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: GENETIC

Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

Interventions

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.

Intervention Type: BIOLOGICAL

Placebo

Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

Intervention Type: 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 10\^8 cells. The injections will be administered following completion of CABG surgery.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Johns Hopkins University Specialized Center for Cell Based Therapy

OTHER

Sponsor Role: collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

Joshua M Hare

OTHER

Sponsor Role: lead

Responsible Party

Joshua M Hare

Director, Interdisciplinary Stem Cell Institute

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joshua M. Hare, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Gary Gerstenblith, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

John V. Conte, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Steven P. Schulman, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

University of Miami Miller School of Medicine

Miami, Florida, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24565698 (View on PubMed)

Other Identifiers

U54HL081028

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20070598

Identifier Type: -

Identifier Source: org_study_id