- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00531921
Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival
Correlation of Donor Proinflammatory mRNA Profiles With Early Outcomes of Thoracic and Abdominal Transplantation
Aperçu de l'étude
Statut
Description détaillée
Inflammation and injuries to transplanted organs during the immediate post-operative period may be linked to early organ dysfunction and higher rates of transplant rejection in the recipient. Currently, mRNA expression of proinflammatory genes in donor tissues is thought to be a risk factor for early organ transplant dysfunction, increased expression of the recipients cell-mediated immunity genes, and organ rejection. The purpose of this study is to test the association between proinflammatory mRNA expression in donor samples and subsequent development of early organ dysfunction in kidney, lung, and liver transplant recipients. This study will also test the effects of proinflammatory mediators expressed in the transplanted organ pre- and post-reperfusion on organ rejection and genes expressed in cell mediated immune responses. This will be achieved by identifying the proinflammatory immune responses and their mechanisms.
This study will consist of up to 11 study visits over a period of 2 years. The baseline visit will occur 24 hours prior to organ transplantation. Follow-up visits will occur daily for Days 1 to 3 (for lung transplant recipients only) and on Day 7, Week 6, and Months 3, 6, 9, 12, 18, and 24 post-transplant. At the baseline visit, a physical exam, medical history, demographics, vital signs measurements, blood collection, and collection of donor tissue sample will occur. For most or all other study visits, medication and adverse events tracking and blood collection will occur. Depending on the transplant type, participants will undergo the following procedures:
- Heart: Participants will undergo a heart biopsy that is part of standard clinical care following a heart transplant. An echocardiogram and an electrocardiogram will occur at most visits.
- Kidney: Renal biopsies will be performed 1 hour after reperfusion at the time of surgery. Urine collection will occur at most visits.
- Liver: Liver biopsies will be performed at the time of procurement and within 1 hour of reperfusion.
- Lung: Participants will undergo bronchoalveolar lavage that is part of standard clinical care following a lung transplant. A chest x-ray, an arterial blood gas test, a pulmonary function test, and 6-minute walking test will occur at some visits.
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Illinois
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Chicago, Illinois, États-Unis, 60611
- Northwestern Memorial Hospital (kidney and liver)
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New York
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Ithaca, New York, États-Unis, 14850
- Cornell University Medical College (kidney)
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New York, New York, États-Unis, 10032
- Columbia University (lung and liver)
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis, 19104
- University of Pennsylvania (heart, kidney, liver, lung)
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Wisconsin
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Madison, Wisconsin, États-Unis, 53706
- University of Wisconsin (heart and lung)
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria for all participants:
- Received single lung, heart, kidney, or liver transplant
- Specimens of donor tissues have been collected
- Parent or guardian willing to provide informed consent, if applicable
Inclusion Criteria for Kidney or Liver Transplant Participants:
- 70 years old or younger
Inclusion Criteria for Heart or Lung Transplant Participants:
- Between 16 and 70 years old
Exclusion Criteria for All Participants:
- Previous solid organ transplant
- Need for combined organ transplant
- HIV or hepatitis C virus infection
- Recipient of an organ from a hepatitis C virus-infected donor
- Clinical evidence of systemic bacterial infection in the recipient at the time of transplantation
- Living donor transplant recipient of either a kidney, liver, or lung
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Kidney transplants
patients from 5 specific sites
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Liver transplants
patients from 5 specific sites
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Heart transplants
patients from 5 specific sites
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Lung transplants
patients from 5 specific sites
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
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Association between proinflammatory mRNA expression in donor samples and subsequent development of early organ dysfunction in the immediate period following transplantation
Délai: Within first 7 days after transplant
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Within first 7 days after transplant
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Association of mRNA expression of proinflammatory mediatros in the transplanted organ in the immediate pre and post-reperfusion period with subsequent incidence of acute rejection and expression of genes involved in cell mediated immunity
Délai: 12 months after transplant
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12 months after transplant
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Collaborateurs et enquêteurs
Collaborateurs
Les enquêteurs
- Chercheur principal: Abraham Shaked, MD, PhD, University of Pennsylvania Medical Center
Publications et liens utiles
Publications générales
- Jiang S, Lechler RI. CD4+CD25+ regulatory T-cell therapy for allergy, autoimmune disease and transplant rejection. Inflamm Allergy Drug Targets. 2006 Dec;5(4):239-42. doi: 10.2174/187152806779010981.
- Zheng XX, Sanchez-Fueyo A, Sho M, Domenig C, Sayegh MH, Strom TB. Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity. 2003 Oct;19(4):503-14. doi: 10.1016/s1074-7613(03)00259-0.
- Kaplan B, Srinivas TR, Meier-Kriesche HU. Factors associated with long-term renal allograft survival. Ther Drug Monit. 2002 Feb;24(1):36-9. doi: 10.1097/00007691-200202000-00007.
- Lande JD, Patil J, Li N, Berryman TR, King RA, Hertz MI. Novel insights into lung transplant rejection by microarray analysis. Proc Am Thorac Soc. 2007 Jan;4(1):44-51. doi: 10.1513/pats.200605-110JG.
- Fox-Marsh A, Harrison LC. Emerging evidence that molecules expressed by mammalian tissue grafts are recognized by the innate immune system. J Leukoc Biol. 2002 Mar;71(3):401-9.
- Isobe M, Suzuki J. New approaches to the management of acute and chronic cardiac allograft rejection. Jpn Circ J. 1998 May;62(5):315-27. doi: 10.1253/jcj.62.315.
- Reding R, Gras J, Truong DQ, Wieers G, Latinne D. The immunological monitoring of alloreactive responses in liver transplant recipients: a review. Liver Transpl. 2006 Mar;12(3):373-83. doi: 10.1002/lt.20704.
- Cantu E, Lederer DJ, Meyer K, Milewski K, Suzuki Y, Shah RJ, Diamond JM, Meyer NJ, Tobias JW, Baldwin DA, Van Deerlin VM, Olthoff KM, Shaked A, Christie JD; CTOT Investigators. Gene set enrichment analysis identifies key innate immune pathways in primary graft dysfunction after lung transplantation. Am J Transplant. 2013 Jul;13(7):1898-904. doi: 10.1111/ajt.12283. Epub 2013 May 24.
- Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Autres numéros d'identification d'étude
- DAIT CTOT-03
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Essais cliniques sur Transplantation hépatique
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Abramson Cancer Center of the University of PennsylvaniaRetiréPatients cancéreux subissant une greffe de cellules souches (RCT of ACP for Transplant)