Ignite Creation Date:
2025-12-24 @ 10:51 PM
Ignite Modification Date:
2026-02-19 @ 9:00 AM
Study NCT ID:
NCT05712369
Status:
COMPLETED
Last Update Posted:
2024-11-29
First Post:
2023-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
B Cells in Idiopathic Nephrotic Syndrome
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Study Overview
Official Title:
Phenotype and Function of Reconstituting B-cells in Steroid Dependent or Frequently Relapsing Nephrotic Syndrome After B-cell Depletion: Insight Into the Disease Pathogenesis and Identification of Predictors of Relapse
Status:
COMPLETED
Status Verified Date:
2024-11
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:
BLADE
Brief Summary:
The main aim of the present study is to determine whether reconstitution of different B-cell subpopulations can predict relapse after treatment with B-cell depleting antibodies in adult with NS, and whether specific B- or T-cell anomalies (as well as dysregulation of other circulating immune cell subsets) may play a role in the disease pathogenesis of SDNS and FRNS.
Detailed Description:
The role of the immune system in Idiopathic Nephrotic Syndrome (INS) of Minimal Change Disease (MCD), Mesangial proliferative Glomerulonephritis (MesGN) or Focal and Segmental Glomerulosclerosis (FSGS) has been widely investigated. However, among immune cell populations, a major player in disease pathogenesis was never found.
The efficacy of B cell depleting therapy with anti-CD20 monoclonal antibodies suggests that B lymphocytes may play a pivotal role.
Preliminary data suggest that memory B cells may be the responsible of the Nephrotic Syndrome (NS) relapse after rituximab treatment in children with Steroid Dependent Nephrotic Syndrome (SDNS) or Frequently-Relapsin gnephrotic Syndrome (FRNS), enforcing the role of the B cell lineage in the disease pathogenesis.
NS is a severe glomerular disease affecting more frequently children and young adult. It is characterized by edema, heavy proteinuria and hypoalbuminemia, the clinical counterpart of the alteration of the selective glomerular permeability barrier. Despite extensive investigation, the mechanism and the immune cell population responsible for the disruption of glomerular filtration barrier and, consequently, of the development of proteinuria is still not clearly defined. However, the efficacy of the different immunosuppressive approaches including prednisone and anti-CD20 antibodies in the treatment of NS strongly suggests a central role of the immune system, in particular the role of B cells in the pathogenesis SDNS. Recent evidence indicates that, after B cell depletion, the delayed reconstitution of the switched memory B cells in children with SDNS was significantly and independently protective against relapse. These results suggest that recovery of switched memory B-cells after anti-CD20 therapies could be a useful predictor of subsequent relapse of the NS in SDNS and FRNS patients, and that memory B-cells may play a role in the pathogenesis of SDNS or FRNS in children.
The efficacy of B cell depleting therapy with anti-CD20 monoclonal antibodies suggests that B lymphocytes may play a pivotal role.
Preliminary data suggest that memory B cells may be the responsible of the Nephrotic Syndrome (NS) relapse after rituximab treatment in children with Steroid Dependent Nephrotic Syndrome (SDNS) or Frequently-Relapsin gnephrotic Syndrome (FRNS), enforcing the role of the B cell lineage in the disease pathogenesis.
NS is a severe glomerular disease affecting more frequently children and young adult. It is characterized by edema, heavy proteinuria and hypoalbuminemia, the clinical counterpart of the alteration of the selective glomerular permeability barrier. Despite extensive investigation, the mechanism and the immune cell population responsible for the disruption of glomerular filtration barrier and, consequently, of the development of proteinuria is still not clearly defined. However, the efficacy of the different immunosuppressive approaches including prednisone and anti-CD20 antibodies in the treatment of NS strongly suggests a central role of the immune system, in particular the role of B cells in the pathogenesis SDNS. Recent evidence indicates that, after B cell depletion, the delayed reconstitution of the switched memory B cells in children with SDNS was significantly and independently protective against relapse. These results suggest that recovery of switched memory B-cells after anti-CD20 therapies could be a useful predictor of subsequent relapse of the NS in SDNS and FRNS patients, and that memory B-cells may play a role in the pathogenesis of SDNS or FRNS in children.
Study Oversight
Has Oversight DMC:
False
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?:
False
Is an FDA AA801 Violation?: