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

19 sierpnia 2019 zaktualizowane przez: Joshua M Hare

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).

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

9

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Stany Zjednoczone
    • Florida
      • Miami, Florida, Stany Zjednoczone, 33136
        • University of Miami Miller School of Medicine
    • Maryland
      • Baltimore, Maryland, Stany Zjednoczone, 21205
        • Johns Hopkins University School Of Medicine

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

21 lat do 80 lat (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Podwójnie

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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
Biologiczny: 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.
Eksperymentalny: Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
Biologiczny: 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.
Komparator placebo: (3) Placebo
Participants will receive placebo injections
Genetyczny: Placebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of Patients With Serious Adverse Events
Ramy czasowe: 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.
12 Months

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Change in Infarct Scar Size (ISS) Over 18 Month Period
Ramy czasowe: 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.
Baseline, 6 Months, 18 Months
Left Ventricular Function (LVF) in Region of MSC Injection
Ramy czasowe: 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.
Assessed at Baseline and 18 Months
Regional Left Ventricular Wall Thickening
Ramy czasowe: Assessed at Baseline and 18 months
Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI.
Assessed at Baseline and 18 months
Left Ventricular End Diastolic Wall Thickness
Ramy czasowe: 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.
Assessed at Baseline and 18 months
Change in Left Ventricular End Diastolic and Systolic Volume
Ramy czasowe: Baseline, 6 Months, 18 Months
Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram.
Baseline, 6 Months, 18 Months
Change in Left Ventricular Ejection Fraction
Ramy czasowe: 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.
Baseline to 6 Months, Baseline to 18 Months
Change in Peak Volume Oxygen
Ramy czasowe: 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
Baseline, 6 Months, 18 Months
Change in Six Minute Walk Test
Ramy czasowe: Baseline, 6 Months, 18 Months
Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months
Baseline, 6 Months, 18 Months
Change in NYHA Functional Class
Ramy czasowe: 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
Baseline to 6 Months, 6 months to 18 Months
Minnesota Living With Heart Failure Questionnaire Scores
Ramy czasowe: 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.
Assessed at 6 Months and 18 Months
Incidence of Major Adverse Cardiac Events (MACE)
Ramy czasowe: 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.
18 Months
Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings
Ramy czasowe: 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.
Assessed at 6 Months, 12 Months, and 18 Months
Change in Pulmonary Function
Ramy czasowe: 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)
Baseline, 6 Months, 12 Months, 18 Months
Serial Troponin Values (ng/mL)
Ramy czasowe: 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
Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG
Creatinine Kinase - Muscle/Brain (MB) (ng/mL)
Ramy czasowe: 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
Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG
Number of Clinically Significant Laboratory Values
Ramy czasowe: 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.
18 Months
Rate of Treatment Emergent Adverse Events
Ramy czasowe: 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
Assessed at 6 Months, 12 Months, and 18 Months
Number of Abnormal Echocardiogram Readings 2 Days Post CABG.
Ramy czasowe: 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.
Day 2

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Joshua M Hare

Współpracownicy

National Heart, Lung, and Blood Institute (NHLBI)
The Emmes Company, LLC
Johns Hopkins University Specialized Center for Cell Based Therapy

Śledczy

  • Główny śledczy: Joshua M. Hare, MD, University of Miami
  • Główny śledczy: Gary Gerstenblith, MD, Johns Hopkins University
  • Główny śledczy: John V. Conte, MD, Johns Hopkins University
  • Główny śledczy: Steven P. Schulman, MD, Johns Hopkins University

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 listopada 2007

Zakończenie podstawowe (Rzeczywisty)

1 czerwca 2011

Ukończenie studiów (Rzeczywisty)

1 czerwca 2011

Daty rejestracji na studia

Pierwszy przesłany

2 stycznia 2008

Pierwszy przesłany, który spełnia kryteria kontroli jakości

3 stycznia 2008

Pierwszy wysłany (Oszacować)

8 stycznia 2008

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

10 września 2019

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

19 sierpnia 2019

Ostatnia weryfikacja

1 sierpnia 2019

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 20070598
  • U54HL081028 (Grant/umowa NIH USA)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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