Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

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

19 agosto 2019 aggiornato da: 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).

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

9

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Florida
      • Miami, Florida, Stati Uniti, 33136
        • University of Miami Miller School of Medicine
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21205
        • Johns Hopkins University School of Medicine

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 21 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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
Biologico: 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.
Sperimentale: Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
Biologico: 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.
Comparatore placebo: (3) Placebo
Participants will receive placebo injections
Genetico: Placebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Patients With Serious Adverse Events
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in Infarct Scar Size (ISS) Over 18 Month Period
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Joshua M Hare

Collaboratori

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

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 novembre 2007

Completamento primario (Effettivo)

1 giugno 2011

Completamento dello studio (Effettivo)

1 giugno 2011

Date di iscrizione allo studio

Primo inviato

2 gennaio 2008

Primo inviato che soddisfa i criteri di controllo qualità

3 gennaio 2008

Primo Inserito (Stima)

8 gennaio 2008

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

10 settembre 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

19 agosto 2019

Ultimo verificato

1 agosto 2019

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 20070598
  • U54HL081028 (Sovvenzione/contratto NIH degli Stati Uniti)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Trapianto di cellule staminali

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Qatar

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

3
Sottoscrivi