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Trial record 19 of 944 for:    stem cells | Studies With Results

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00587990
Recruitment Status : Terminated (Difficulty in recruitment.)
First Posted : January 8, 2008
Results First Posted : April 2, 2015
Last Update Posted : September 10, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University Specialized Center for Cell Based Therapy
The Emmes Company, LLC
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

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).

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

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.


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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
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
Genetic: Placebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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


  10. 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.

  11. 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.

  12. 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.


  13. 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)

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
Joshua M Hare
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University Specialized Center for Cell Based Therapy
The Emmes Company, LLC
Investigators
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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

Publications of Results:
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Responsible Party: Joshua M Hare, Director, Interdisciplinary Stem Cell Institute, University of Miami
ClinicalTrials.gov Identifier: NCT00587990     History of Changes
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joshua M Hare, University of Miami:
Chronic Ischemic Left Ventricular Dysfunction
Additional relevant MeSH terms:
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Ventricular Dysfunction
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases