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

19 août 2019 mis à jour par: 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).

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

9

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Florida
      • Miami, Florida, États-Unis, 33136
        • University of Miami Miller School of Medicine
    • Maryland
      • Baltimore, Maryland, États-Unis, 21205
        • Johns Hopkins University School of Medicine

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

21 ans à 80 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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
Biologique: 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.
Expérimental: Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
Biologique: 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.
Comparateur placebo: (3) Placebo
Participants will receive placebo injections
Génétique: Placebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Patients With Serious Adverse Events
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Change in Infarct Scar Size (ISS) Over 18 Month Period
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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
Délai: 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.
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Joshua M Hare

Collaborateurs

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

Les enquêteurs

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

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 novembre 2007

Achèvement primaire (Réel)

1 juin 2011

Achèvement de l'étude (Réel)

1 juin 2011

Dates d'inscription aux études

Première soumission

2 janvier 2008

Première soumission répondant aux critères de contrôle qualité

3 janvier 2008

Première publication (Estimation)

8 janvier 2008

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

10 septembre 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

19 août 2019

Dernière vérification

1 août 2019

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 20070598
  • U54HL081028 (Subvention/contrat des NIH des États-Unis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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