Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06351488
Status:
RECRUITING
Last Update Posted:
2024-04-08
First Post:
2024-04-02
Brief Title:
Detection of Circulating Kidney DNA in Kidney Transplant Patients Facing an Episode of Graft Rejection
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Detection of Circulating Kidney DNA in Kidney Transplant Patients Facing an Episode of Graft Rejection
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DART-RREGREF
Brief Summary:
In France 3500 kidney transplants are carried out per year and 40000 people succeed in 2019 with a kidney transplant Despite regular medical monitoring nearly 30 of transplant patients will develop rejection Currently only solid biopsy of the graft makes it possible to establish the diagnosis of graft rejection and to characterize its cellular origin based on the Banff classification
Several studies have shown the possibility of identifying the tissue origin of DNA circulating in the blood in healthy subjects on the basis of the epigenetic properties of circulating DNA In addition in kidney transplant subjects an increase in the quantity of circulating DNA originating from the graft in the blood and urine has been shown as well as an increase in urinary chemokine levels during renal dysfunction notably dismiss Thus the company CGenetix in partnership with INSERM units 1155 and 1151 is developing a method to identify and characterize kidney transplant rejection early through the detection of epigenetic biomarkers on circulating DNA targeting different fractions of the kidney glomerular tubular peritubular capillary and vascular The main objective is to study the diagnostic performance of the quantity of DNA of renal origin in kidney transplant patients in the blood and in the urine expressed in copiesml for the diagnosis of type Rejection mediated by kidneys antibody ABMR established by kidney graft biopsy gold standard and according to the Banff 2022 classification
Several studies have shown the possibility of identifying the tissue origin of DNA circulating in the blood in healthy subjects on the basis of the epigenetic properties of circulating DNA In addition in kidney transplant subjects an increase in the quantity of circulating DNA originating from the graft in the blood and urine has been shown as well as an increase in urinary chemokine levels during renal dysfunction notably dismiss Thus the company CGenetix in partnership with INSERM units 1155 and 1151 is developing a method to identify and characterize kidney transplant rejection early through the detection of epigenetic biomarkers on circulating DNA targeting different fractions of the kidney glomerular tubular peritubular capillary and vascular The main objective is to study the diagnostic performance of the quantity of DNA of renal origin in kidney transplant patients in the blood and in the urine expressed in copiesml for the diagnosis of type Rejection mediated by kidneys antibody ABMR established by kidney graft biopsy gold standard and according to the Banff 2022 classification
Detailed Description:
Kidney transplantation remains the standard treatment for patients with end-stage renal disease It provides the patient with a better quality of life1 and a better chance of survival for a reduced cost of care compared to dialysis While more than 3000 kidney transplants are carried out each year in France more than 20000 candidates are registered on the transplant waiting list revealing a severe shortage of grafts Limiting the degradation of the kidney graft would make it possible to avoid the return of patients to dialysis and limit the shortage of grafts
At the diagnostic level routine monitoring of graft functionality after kidney transplantation is based on the use of non-specific markers such as serum creatinine allowing the 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 evaluating graft status The anatomopathological diagnosis of renal graft dysfunction is based on the Banff classification and makes it possible to examine the immune infiltrate and cellular lesions of the graft in order to make a diagnosis on 1-the presence of graft rejection or other attacks and 2- the anatomical compartment affected by the pathology tubular vascular interstitial or glomerular
The start-up CGenetix offers an original approach to predict and characterize renal graft rejectiondysfunction based on the quantification of epigenetic signatures present on donor-cell-free DNA In 2018 Moss et al are developing a deconvolution model capable of identifying the tissue origin of circulating DNA by taking advantage of its epigenetic properties The study confirmed that the free DNA circulating in healthy subjects comes mainly from blood cells and endothelial cells but not from kidney cells
In this protocol 319 kidney transplant patients will be recruited from the Renal Transplantation departments of Pitié-Salpêtrière and Necker Patients will be recruited into the study at the time of their hospitalization for renal biopsy for causeindication inclusion visit Urine and blood samples will be taken within 24 hours before the kidney biopsy is performed
The quantities of circulating DNA of renal origin total kidney biomarkers x2 specific tubules x2 specific glomeruli x2 specific peritubular capillaries x2 and specific arteriolar capillaries x2 will be determined by digital PCR and expressed in copyml in blood and urine samples
The main evaluation criterion of the research is the area under the ROC curve of the ABMR type rejection prediction models according to renal biopsy and with as covariates of interest the quantities of circulating DNA of renal origin kidney biomarkers total x2 specific tubules x2 specific glomeruli x2 specific peritubular capillaries x2 and specific arteriolar capillaries x2 determined by digital PCR and expressed in copyml in blood and urine The final objective of this study protocol consists of i prospectively validating the performance of the diagnostic test proposed by CGenetix and its partners INSERM 1155 and 1151 and urinary chemokines to non-invasively diagnose acute renal graft rejection and ii study its ability to diagnose the different types of renal transplant rejection ABMR TCMR Mixed Without rejection The research hypotheses are i an AUC 080 Sensitivity and specificity 80 for each biomarker taken individually ii an AUC 085 Sensitivity and specificity 85 for the multimodal prediction model
At the diagnostic level routine monitoring of graft functionality after kidney transplantation is based on the use of non-specific markers such as serum creatinine allowing the 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 evaluating graft status The anatomopathological diagnosis of renal graft dysfunction is based on the Banff classification and makes it possible to examine the immune infiltrate and cellular lesions of the graft in order to make a diagnosis on 1-the presence of graft rejection or other attacks and 2- the anatomical compartment affected by the pathology tubular vascular interstitial or glomerular
The start-up CGenetix offers an original approach to predict and characterize renal graft rejectiondysfunction based on the quantification of epigenetic signatures present on donor-cell-free DNA In 2018 Moss et al are developing a deconvolution model capable of identifying the tissue origin of circulating DNA by taking advantage of its epigenetic properties The study confirmed that the free DNA circulating in healthy subjects comes mainly from blood cells and endothelial cells but not from kidney cells
In this protocol 319 kidney transplant patients will be recruited from the Renal Transplantation departments of Pitié-Salpêtrière and Necker Patients will be recruited into the study at the time of their hospitalization for renal biopsy for causeindication inclusion visit Urine and blood samples will be taken within 24 hours before the kidney biopsy is performed
The quantities of circulating DNA of renal origin total kidney biomarkers x2 specific tubules x2 specific glomeruli x2 specific peritubular capillaries x2 and specific arteriolar capillaries x2 will be determined by digital PCR and expressed in copyml in blood and urine samples
The main evaluation criterion of the research is the area under the ROC curve of the ABMR type rejection prediction models according to renal biopsy and with as covariates of interest the quantities of circulating DNA of renal origin kidney biomarkers total x2 specific tubules x2 specific glomeruli x2 specific peritubular capillaries x2 and specific arteriolar capillaries x2 determined by digital PCR and expressed in copyml in blood and urine The final objective of this study protocol consists of i prospectively validating the performance of the diagnostic test proposed by CGenetix and its partners INSERM 1155 and 1151 and urinary chemokines to non-invasively diagnose acute renal graft rejection and ii study its ability to diagnose the different types of renal transplant rejection ABMR TCMR Mixed Without rejection The research hypotheses are i an AUC 080 Sensitivity and specificity 80 for each biomarker taken individually ii an AUC 085 Sensitivity and specificity 85 for the multimodal prediction model
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None