Ignite Creation Date:
2025-12-24 @ 3:28 PM
Ignite Modification Date:
2025-12-26 @ 9:01 PM
Study NCT ID:
NCT06026592
Status:
RECRUITING
Last Update Posted:
2025-09-24
First Post:
2023-08-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D058186', 'term': 'Acute Kidney Injury'}], 'ancestors': [{'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-09-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2026-07-09', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-23', 'studyFirstSubmitDate': '2023-08-30', 'studyFirstSubmitQcDate': '2023-08-30', 'lastUpdatePostDateStruct': {'date': '2025-09-24', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2023-09-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-07-02', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Amount of renal circulating cell-free DNA', 'timeFrame': '6 hours before kidney transplantation and 12 to 24 after transplantation surgery', 'description': 'The amount of renal-cell-free DNA (glomerular and tubular markers) will be measured 6 hours before the kidney transplant is performed and 12-24 hours after the kidney transplant by digital multiplex PCR'}], 'secondaryOutcomes': [{'measure': 'Estimating the inter-individual variations of the free circulating methylome of renal origin in patients with end-stage chronic insufficiency', 'timeFrame': '6 hours before kidney transplantation and 12 to 24 after transplantation surgery', 'description': 'The amount of renal-cell-free DNA (glomerular and tubular markers) measured will be compared between individuals.'}, {'measure': 'Identify by a method without a priori (methyl seq) specific markers of acute renal injury in terms of epigenetic signature', 'timeFrame': '6 hours before kidney transplantation and 12 to 24 after transplantation surgery', 'description': 'Comparison of two biomarkers quantification methods (whole genome methyl-Sequencing and multiplex digital-PCR)'}, {'measure': 'Study the statistical association between the presence of free circulating methylated sequences of renal origin and the resumption of graft function', 'timeFrame': '7 day after the transplant', 'description': 'Comparison of circulating free methylome of renal origin between the groups of patients with immediate recovery of function and delayed recovery of function (defined on the performance of a dialysis session in the first 7 days and on the reduction ratio serum creatinine between the 1st and 2nd day after the transplant).'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Epigenetic', 'Renal cell-free DNA', 'Transplantation', 'biomarkers'], 'conditions': ['Acute Kidney Injury', 'Renal Transplantation']}, 'descriptionModule': {'briefSummary': 'Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential diagnostic tool to monitor the rejection status of the kidney transplant. It has been suggested that dd-cfDNA is increasing in the blood of kidney transplant patient presenting a graft rejection. In this project, investigators proposed a different approach to predict and characterize kidney transplant rejection/dysfunction based on the quantification of epigenetic signatures present on the donor-cell-free DNA. In 2018, Moss et al. develops a deconvolution model capable of identifying the tissue origin of circulating DNA by taking advantage of its epigenetic properties. The study confirmed that the cell-free DNA circulating in healthy subjects comes mainly from blood cells and endothelial cells, but not from kidney cells.\n\nIn this study, researchers investigate the evolution of blood renal-specific cell-free DNA amount in patient with chronic kidney disease before and after the transplantation surgery by testing a set of renal-specific epigenetic markers. The purpose of this study is to identify the biological noise of "native kidney" on renal-specific cell-free DNA and to compare it with signal coming from "transplanted kidney".', 'detailedDescription': 'At the diagnostic level, routine monitoring of graft functionality after kidney transplantation relies on the use of non-specific markers, such as serum creatinine (allowing estimation of glomerular filtration rate or GFR) and proteinuria. Definitive diagnosis of renal allograft dysfunction still requires invasive allograft biopsy, which remains the gold standard for assessing graft status. The histopathological diagnosis of renal graft dysfunction is based on the Banff classification and makes it possible to examine the immune infiltrate and the cellular lesions of the graft to make a precise diagnosis. However, Renal biopsy has certain limitations: 1/ It is invasive for the patient, with associated complications, mainly hemorrhagic in 1 to 3.5% of cases; 2/ Its effectiveness in predicting early rejection (3 months) post-transplant remains controversial. A lack of patient benefit has been proven by several studies for screening biopsy; 3/ Histological analysis is subject to intra- and inter-observer variations; and 4/ it is an expensive examination due to the medical time required to perform and interpret the biopsy.\n\nThe "donor-cell-free DNA (dd-cfDNA)" has been suggested as a diagnostic tool at the service of the graft. Analyzes based on molecular signatures on the circulating DNA of the donor (Single Polymorphism Nucleotide (SNP)) have made it possible to discriminate the circulating cell-free DNA from the transplanted kidney (from the donor) from the circulating cell-free DNA specific to the recipient. Data from several studies suggest that blood dd-cfDNA levels can detect rejection in heart, lung, liver and kidney allografts. First studied by multiplex qPCR and then NGS technologies, the SNPs present on the dd-cfDNA were then quantified by digital PCR techniques.\n\nIn this study, investigators proposed a different approach to predict and characterize kidney transplant rejection/dysfunction based on the quantification of epigenetic signatures present on the donor-cell-free DNA. In 2018, Moss et al. develops a deconvolution model capable of identifying the tissue origin of circulating DNA by taking advantage of its epigenetic properties. The study confirmed that the cell-free DNA circulating in healthy subjects comes mainly from blood cells and endothelial cells, but not from kidney cells. In 2023, Loyfer et al. proposed a methylation atlas of more than 200 cells type and suggested that each cell has its own epigenetic signature that can be study in cell-free DNA.\n\nIn this study, researchers investigate the evolution of blood renal-specific cell-free DNA amount in patient with chronic kidney disease before and after the transplantation surgery by testing a set of renal-specific epigenetic markers. The purpose of this study is to identify the biological noise of "native kidney" on renal-specific cell-free DNA and to compare it with signal coming from "transplanted kidney". Researchers hypothesize that the biological noise from "native kidney" in chronic kidney diseases is negligible compared to that of the post-transplantation graft.\n\nTo investigate this hypothesis, investigators collect blood samples before and after transplant surgery to quantify kidney-specific cell-free DNA markers. They also proposed to quantify cell-free DNA markers of graft perfusion fluid to validate the specificity of renal markers and to study graft tissue damage during organ transport. Each renal-cell-free DNA sample is quantified by a proprietary technologies using a multiplex digital-PCR assay.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Adult subjects with end-stage renal disease about to receive a kidney transplant from a deceased donor.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years old\n* With end-stage renal failure\n* Summoned for a kidney transplant at Pitié Salpêtrière Hospital\n* Having been informed of the study and not objecting to the study having given free and informed written consent for the genetic analysis\n* Benefiting from a social security scheme (excluding AME)\n\nExclusion Criteria:\n\nUnder legal protective measures (curatorship or guardianship, under judicial safeguard).'}, 'identificationModule': {'nctId': 'NCT06026592', 'acronym': 'DART-REIN', 'briefTitle': 'Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients', 'orgStudyIdInfo': {'id': 'APHP230298'}}, 'armsInterventionsModule': {'interventions': [{'name': 'determination of circulating biomarkers of renal origin circulating biomarkers of renal origin', 'type': 'GENETIC', 'description': 'The extracted circulating DNA will be extracted and converted using the methylation kit. Finally, circulating DNA will be analyzed using the PCR mix developed by CGenetix, quantifying tubular and glomerular biomarkers (patented technology).'}]}, 'contactsLocationsModule': {'locations': [{'zip': '75013', 'city': 'Paris', 'state': 'Île-de-France Region', 'status': 'RECRUITING', 'country': 'France', 'contacts': [{'name': 'Sarah DROUIN, MD, PhD', 'role': 'CONTACT', 'email': 'sarah.drouin@aphp.fr', 'phone': '+33 1 42 17 71 73'}, {'name': 'Geoffroy POULET, PhD', 'role': 'CONTACT', 'email': 'geoffroy.poulet@cgenetix.com', 'phone': '+33 6 67 77 23 94'}], 'facility': 'Pitié-Salpétriêre Hospital', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'centralContacts': [{'name': 'Sarah Dr DROUIN, MD-PhD', 'role': 'CONTACT', 'email': 'sarah.drouin@aphp.fr', 'phone': '+33 1 42 17 71 73', 'phoneExt': '+33'}, {'name': 'Geoffroy Dr POULET, PhD', 'role': 'CONTACT', 'email': 'Geoffroy.poulet@cgenetix.com', 'phone': '+33 6 67 77 23 94', 'phoneExt': '+33'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'ICF'], 'timeFrame': 'Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor', 'ipdSharing': 'YES', 'description': 'The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l\\'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.\n\nConsultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.', 'accessCriteria': 'Researchers who provide a methodologically sound proposal.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}