Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06443034
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-05
First Post:
2024-05-28
Brief Title:
Predictive Determinants of Nephrotic Syndrome Remission in Patients With At-risk Polymorphism of APOL1
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Predictive Determinants of Nephrotic Syndrome Remission in Patients With Focal Segmental Glomerulosclerosis or Minimal Change Disease and At-risk Polymorphism of APOL1 Gene
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
NEPHROL1
Brief Summary:
This is a multicentric retrospective observational cohort study
As primary objective the study aims to evaluate the factors associated with nephrotic syndrome remission in patient with nephrotic syndrome biopsy-prove minimal change disease or focal segmental glomerulosclerosis and an at-risk variant of the APOL1 gene
As secondary objectives this study aims
To evaluate the benefit of corticosteroids in obtaining the remission of nephrotic syndrome
To identify the predictors of complete renal remission of nephrotic syndrome
To evaluate the benefit of corticosteroids in reducing the incidence of end-stage renal disease
To assess the adverse events of corticosteroids in patients treated with corticosteroids
As primary objective the study aims to evaluate the factors associated with nephrotic syndrome remission in patient with nephrotic syndrome biopsy-prove minimal change disease or focal segmental glomerulosclerosis and an at-risk variant of the APOL1 gene
As secondary objectives this study aims
To evaluate the benefit of corticosteroids in obtaining the remission of nephrotic syndrome
To identify the predictors of complete renal remission of nephrotic syndrome
To evaluate the benefit of corticosteroids in reducing the incidence of end-stage renal disease
To assess the adverse events of corticosteroids in patients treated with corticosteroids
Detailed Description:
The APOL1 gene synthesizes Apolipoprotein L1 a transport protein for hydrophobic molecules When this gene presents bi-allelic at risk polymorphisms it has been associated with an increased risk of end-stage renal disease These polymorphisms can be frequent on a population scale affecting up to 32 of patients in some West African countries The pathogenic nature of these variants is now well established and has been highlighted on several occasions notably in HIV-associated nephropathy HIVAN - HIV Associated Nephropathy or more recently in COVID-19-associated nephropathy COVAN - COVID Associated Nephropathy where almost all patients carry APOL1 risk alleles Irrespective of the causative agent nephropathy associated with APOL1 risk variants is regularly revealed by a nephrotic syndrome This syndrome is characterized by generalized edema high-range proteinuria and acute kidney injury The course of the disease is particularly difficult to predict and highly variable with some patients requiring rapid and definitive dialysis while others recover normal renal function without sequelae of proteinuria In addition to this inter-individual variability there is also variability in clinical practice with regard to the use of high-dose corticosteroids to induce disease remission This is largely due to the rarity of the disease in the West and its possible under-diagnosis in developing countries However new drugs specifically targeting APOL1 are currently being developed but their use is currently restricted to studies that exclude the most severe patients In patients with at-risk APOL1 variants and nephrotic syndromes it therefore appears critical to identify the determinants associated with remission of nephropathy to quantify the efficacy of current therapies and to facilitate access to emerging drugs for the most severely ill subjects
The main aim of this study is to evaluate the predictors drug clinical histological or biological parameters associated with nephrotic syndrome remission in patients with nephrotic syndrome biopsy proven focal segmental glomerulosclerosis or minimal change disease and an at-risk variant of the APOL1 gene
Population involved eligible patients will be enrolled if they are more than 18 years old have nephrotic syndrome serum albumin 30 gL and urine protein creatinine ratio 3 gg and biopsy-proven focal segmental glomerulosclerosis or minimal change disease
Data analysis the association of each explanatory variable with the variable remission of nephrotic syndrome will first be assessed using a semi-parametric univariable Cox modelThen a multivariable Cox model will be performed with the explanatory variables associated with the variable remission of nephrotic syndrome with a p value 02 at the Wald test in univariable Cox regression analysis Variables independently associated with remission of nephrotic syndrome will be those with a two-sided p value 005 after stepwise backward elimination in the multivariate model
In order to assess the robustness of our results with the statistical approach the investigators will also conduct association analyses between the predictor variables and the variable of interest using the machine learning analysis known as Random Forrest analysis
As secondary outcomes the association between corticosteroids and nephrotic syndrome remission will be evaluated The association between corticosteroids and end-stage renal disease will also be evaluated as a secondary outcome The third secondary outcome evaluated will be the association between the predictor variables and complete remission of nephrotic syndrome The last secondary outcome will be the assessment of corticosteroids safety evaluated following the common terminology criteria for adverse event version 50
The main aim of this study is to evaluate the predictors drug clinical histological or biological parameters associated with nephrotic syndrome remission in patients with nephrotic syndrome biopsy proven focal segmental glomerulosclerosis or minimal change disease and an at-risk variant of the APOL1 gene
Population involved eligible patients will be enrolled if they are more than 18 years old have nephrotic syndrome serum albumin 30 gL and urine protein creatinine ratio 3 gg and biopsy-proven focal segmental glomerulosclerosis or minimal change disease
Data analysis the association of each explanatory variable with the variable remission of nephrotic syndrome will first be assessed using a semi-parametric univariable Cox modelThen a multivariable Cox model will be performed with the explanatory variables associated with the variable remission of nephrotic syndrome with a p value 02 at the Wald test in univariable Cox regression analysis Variables independently associated with remission of nephrotic syndrome will be those with a two-sided p value 005 after stepwise backward elimination in the multivariate model
In order to assess the robustness of our results with the statistical approach the investigators will also conduct association analyses between the predictor variables and the variable of interest using the machine learning analysis known as Random Forrest analysis
As secondary outcomes the association between corticosteroids and nephrotic syndrome remission will be evaluated The association between corticosteroids and end-stage renal disease will also be evaluated as a secondary outcome The third secondary outcome evaluated will be the association between the predictor variables and complete remission of nephrotic syndrome The last secondary outcome will be the assessment of corticosteroids safety evaluated following the common terminology criteria for adverse event version 50
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