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Stem Cell TransplantationPhase 1/2PROMETHEUSNCT00587990

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

A Phase 1/2 study testing Lower dose mesenchymal stem cell (MSC) injection and Higher dose MSC injection in people with Stem Cell Transplantation and Ventricular Dysfunction, Left, run by Joshua M Hare at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 80 years
What is being tested?
Lower dose mesenchymal stem cell (MSC) injection and Higher dose MSC injection
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
9 participants
Where
2 sitesUnited States
Study dates
Nov 2007to Jun 2011
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21205

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

Other trials in United States

About this study

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)

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).

Read the 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.

Being tested
Lower dose mesenchymal stem cell (MSC) injection, Placebo, Higher dose MSC injection
Keywords
Chronic Ischemic Left Ventricular Dysfunction
Medical subject headings
Ventricular Dysfunction, Left

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lower dose mesenchymal stem cell (MSC) injectionBiological

    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.

  • PlaceboGenetic

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

  • Higher dose MSC injectionBiological

    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.

Study groups in NCT00587990
Study groupRoleWhat they receive
Lower dose mesenchymal stem cell (MSC) injectionExperimentalParticipants will receive lower dose mesenchymal stem cell injections for a total of 2 x 10^7 cells
Receives: Biological: Lower dose mesenchymal stem cell (MSC) injection
Higher dose MSC injectionExperimentalParticipants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
Receives: Biological: Higher dose MSC injection
(3) PlaceboPlacebo comparatorParticipants will receive placebo injections
Receives: Genetic: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 Months

Secondary outcomes (18)

  1. 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.

    Measured: Baseline, 6 Months, 18 Months

  2. 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.

    Measured: Assessed at Baseline and 18 Months

  3. Regional Left Ventricular Wall Thickening

    Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI.

    Measured: Assessed at Baseline and 18 months

  4. 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.

    Measured: Assessed at Baseline and 18 months

  5. Change in Left Ventricular End Diastolic and Systolic Volume

    Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram.

    Measured: Baseline, 6 Months, 18 Months

  6. 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.

    Measured: Baseline to 6 Months, Baseline to 18 Months

  7. 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

    Measured: Baseline, 6 Months, 18 Months

  8. Change in Six Minute Walk Test

    Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months

    Measured: Baseline, 6 Months, 18 Months

  9. 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

    Measured: Baseline to 6 Months, 6 months to 18 Months

  10. 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.

    Measured: Assessed at 6 Months and 18 Months

  11. 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.

    Measured: 18 Months

  12. 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.

    Measured: Assessed at 6 Months, 12 Months, and 18 Months

  13. 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)

    Measured: Baseline, 6 Months, 12 Months, 18 Months

  14. Serial Troponin Values (ng/mL)

    Serial Troponin Values (ng/mL) Values from Baseline to 48 Hours Post CABG

    Measured: Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG

  15. Creatinine Kinase - Muscle/Brain (MB) (ng/mL)

    Creatinine Kinase MB (ng/mL) Values every 12 hours from Baseline to 48 Hours Post CABG

    Measured: Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG

  16. 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.

    Measured: 18 Months

  17. 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

    Measured: Assessed at 6 Months, 12 Months, and 18 Months

  18. 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.

    Measured: Day 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2008 (estimated)
  2. Study startNov 2007
  3. Primary completionJun 2011
  4. Study completionJun 2011

Why it stopped: Difficulty in recruitment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00587990
Sponsor's protocol ID
20070598
Other IDs
U54HL081028
Acronym
PROMETHEUS
Status last verified
Aug 2019
First submitted
2 Jan 2008
Last updated
10 Sep 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 24565698

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lower dose mesenchymal stem cell (MSC) injection and Higher dose MSC injection in people with Stem Cell Transplantation and Ventricular Dysfunction, Left, run by Joshua M Hare at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Serious Adverse Events (time frame: 12 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00587990, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019; AzTrials last refreshed its copy on 6 Nov 2026.

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