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- Essai clinique NCT01985412
Genome Transplant Dynamics: Non-invasive Sequencing-based Diagnosis of Rejection (GTD)
2 octobre 2019 mis à jour par: Kiran Khush, Stanford University
Genome Transplant Dynamics: Non-Invasive Sequencing-Based Diagnosis of Rejection
The purpose of this study is to determine whether shotgun sequencing technology, which can be used to detect donor DNA in recipient plasma, can be used as a rapid, accurate, non-invasive method to detect Acute Cellular Rejection (ACR) after heart transplantation.
Currently, all heart transplant recipients undergo invasive heart biopsies to diagnose ACR.
Thus, there is an ongoing need to monitor patients for the development of acute and chronic rejection, with the primary goal of non-invasive early detection and treatment to prevent organ damage.
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
Previous attempts to develop a non-invasive marker of graft rejection have focused on recipient-specific immune responses, and thus have inherent limitations in both sensitivity and selectivity, especially in distinguishing rejection from infection.
The investigators' goal is to use a novel DNA sequencing technology to develop a rapid, inexpensive, and non-invasive method for monitoring organ transplant recipients for graft rejection.
The investigators' research is driven by the fact that acute and chronic rejection of thoracic organ transplants remain major causes of patient morbidity and mortality, and require intense resource utilization.
The investigators' novel approach is the first to focus on a donor-specific marker of acute rejection.
The investigators will use high throughput next generation sequencing to monitor the proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.
This approach is enabled by the fact that an organ transplant is also effectively a genome transplant, and by monitoring single nucleotide polymorphisms that are specific to the donor's genome (and are not shared with the recipient's genome) one can measure the relative health of the transplanted organ.
The investigators' preliminary studies show that cell-free donor DNA levels in the serum of heart transplant recipients increase prior to diagnosis of acute rejection by endomyocardial biopsy, but remain at stable low levels in the absence of acute rejection.
Type d'étude
Observationnel
Inscription (Réel)
65
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
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California
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Santa Clara, California, États-Unis, 95051
- Kaiser Permanente Northern California
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Stanford, California, États-Unis, 94305
- Stanford University Hospital and Clinics
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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
- Enfant
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
Stanford and Lucille Packard adult and pediatric, lung or heart transplant recipients and Kaiser adult heart transplant recipients.
La description
Inclusion Criteria:
- All ages of heart or lung transplant recipients
- Recipients of re-do heart or re-do lung transplants
Exclusion Criteria:
- Patients wait-listed for multiple organ transplantation (e.g. heart-kidney, heart-liver, heart and lung.)
- Unable or unwilling to return to Stanford for biopsy and follow-up procedures
- Followed by Palo Alto VA Hospital after transplant surgery (VA patients are transplanted at Stanford, but all subsequent clinical care is performed at VA hospitals)
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
Cohortes et interventions
Groupe / Cohorte |
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Adult Heart Transplant Recipients
Patients >18 yrs old that received a heart-only transplant and are followed at Stanford Hospital
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Pediatric Heart Transplant Recipients
Patients <18 yrs old that received a heart-only transplant and are followed at Lucile Packard Hospital
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Adult Lung Transplant Recipients
Patients >18 yrs old that received a lung-only transplant and are followed at Stanford Hospital
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Pediatric Lung Transplant Recipients
Patients <18 yrs old that received a lung-only transplant and are followed at Lucile Packard Hospital
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Kaiser Adult Heart Transplant Recipients
Patients >18 yrs old that received a heart-only transplant at Stanford Hospital but are followed at Kaiser Permanente in Santa Clara
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.
Délai: The outcome measure is assessed for each patient up to 5 years post-transplant. Sampling timepoints include: Days 1, 2, 3, Weeks 1, 2, 4, 6, 8, 10, 12, Months 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and quarterly through year 5
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We will use high throughput next generation sequencing to monitor the proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.
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The outcome measure is assessed for each patient up to 5 years post-transplant. Sampling timepoints include: Days 1, 2, 3, Weeks 1, 2, 4, 6, 8, 10, 12, Months 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and quarterly through year 5
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Kiran Khush, MD MAS FACC, Stanford University Hospital and Clinics
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
- Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28.
- Keller M, Bush E, Diamond JM, Shah P, Matthew J, Brown AW, Sun J, Timofte I, Kong H, Tunc I, Luikart H, Iacono A, Nathan SD, Khush KK, Orens J, Jang M, Agbor-Enoh S. Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD). J Heart Lung Transplant. 2021 Jun;40(6):488-493. doi: 10.1016/j.healun.2021.02.008. Epub 2021 Feb 20.
- Agbor-Enoh S, Jackson AM, Tunc I, Berry GJ, Cochrane A, Grimm D, Davis A, Shah P, Brown AW, Wang Y, Timofte I, Shah P, Gorham S, Wylie J, Goodwin N, Jang MK, Marishta A, Bhatti K, Fideli U, Yang Y, Luikart H, Cao Z, Pirooznia M, Zhu J, Marboe C, Iacono A, Nathan SD, Orens J, Valantine HA, Khush K. Late manifestation of alloantibody-associated injury and clinical pulmonary antibody-mediated rejection: Evidence from cell-free DNA analysis. J Heart Lung Transplant. 2018 Jul;37(7):925-932. doi: 10.1016/j.healun.2018.01.1305. Epub 2018 Jan 31.
- De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, Bernstein D, Valantine HA, Quake SR. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell. 2013 Nov 21;155(5):1178-87. doi: 10.1016/j.cell.2013.10.034.
- De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.
- Vollmers C, De Vlaminck I, Valantine HA, Penland L, Luikart H, Strehl C, Cohen G, Khush KK, Quake SR. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study. PLoS Med. 2015 Oct 14;12(10):e1001890. doi: 10.1371/journal.pmed.1001890. eCollection 2015 Oct.
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 mars 2010
Achèvement primaire (Réel)
29 septembre 2013
Achèvement de l'étude (Réel)
29 septembre 2013
Dates d'inscription aux études
Première soumission
28 mai 2013
Première soumission répondant aux critères de contrôle qualité
8 novembre 2013
Première publication (Estimation)
15 novembre 2013
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
4 octobre 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
2 octobre 2019
Dernière vérification
1 octobre 2019
Plus d'information
Termes liés à cette étude
Mots clés
Autres numéros d'identification d'étude
- 17666
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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