B Cells in Idiopathic Nephrotic Syndrome

NCT05712369 | Completed

• 1 other identifier: BLADE
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephrotic Syndrome

Keywords

Nephrotic syndrome; Steroids, B cells; B cells; Anti-CD20 antibodies

Outcome Measures

Primary Outcomes (7)

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in frequency of circulating B cell subpopulations

  At baseline, 6,9 12 and 24 months after treatment.

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in frequency of circulating T cell

  At baseline, 6,9 12 and 24 months after treatment.

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in NK-cell

  At baseline, 6,9 12 and 24 months after treatment.

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in monocyte

  At baseline, 6,9 12 and 24 months after treatment.

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in dendritic cell subpopulations

  At baseline, 6,9 12 and 24 months after treatment.

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in serum levels of cytokines

  At baseline, 6,9 12 and 24 months after treatment.

• Differences between NS patients who relapse (R) or who achieved sustained remission (NR) after B-cell depleting monoclonal antibody treatment in serum levels of immunoglobulin classes and subclasses

  At baseline, 6,9 12 and 24 months after treatment.

Study Arms (3)

Prospective cohort

EXPERIMENTAL

Patients with INS due to biopsy-proven MCD or FSGS or MesGN candidate to anti-CD20 monoclonal antibodies therapy.

Other: Blood sampling

Retrospective cohort

EXPERIMENTAL

Patients with INS due to biopsy-proven MCD or FSGS or MesGN, treated with anti-CD20 monoclonal antibodies therapy.

Other: Blood sampling

Healthy volunteers cohort

ACTIVE COMPARATOR

Subjects not known to suffer of any significant illness, not assuming any medication or drug on a regular basis.

Other: Blood sampling

Interventions

Blood sampling OTHER

Before the anti-CD20 monoclonal antibodies treatment (e.g. Rituximab/Ofatumumab) and after 6, 9 and 12, 24 months from the first infusion the following blood samples will be collected for the analysis of lymphocyte subpopulations: * 50/100 mL of blood (20 mL for pediatric patients) for Peripheral Blood Mononuclear Cells (PBMCs) isolation. * 8 mL of blood (both adult and pediatric) to obtain serum. Serum will be obtained by standard centrifugation and PBMC will be isolated by Ficoll-Paque® density gradient centrifugation, according to manufacturer's instruction.

Healthy volunteers cohort; Prospective cohort; Retrospective cohort

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female children (≥6 and \<18 years old) and adults.
• Patients with biopsy-proven MCD or FSGS or MesGN candidate to (prospective cohort) or treated with (retrospective cohort) anti-CD20 monoclonal antibodies (when possible) due to INS and fulfilling the following conditions:
• SDNS: defined as two consecutive relapses of the NS during corticosteroid therapy, or within 14 days of ceasing therapy;
• FRNS: defined as two or more relapses within 6 months of initial response, or four or more relapses in any 12-month period; Note: relapse in pediatric patients is defined as a urinary protein to creatinine ratio \> 2000 mg/g or a positive urine dipstick (≥ 3+) for 3 consecutive days; in adult is defined as a urinary protein to creatinine ratio \> 3500 mg/g or by proteinuria \>3.5 g/day after remission has been obtained.
• Patients will be included irrespective of previous (retrospective cohort) or planned (prospective cohort) treatments with anti-CD20 monoclonal antibodies.
• SRNS not associated with known genetic abnormalities of the glomerular barrier consisting in persistent nephrotic-range proteinuria (no complete/partial remission) despite prednisone 1 mg/kg/day or 2 mg/kg every other day for \>4 months (adults) or despite prednisone 60 mg/m2/day or 2 mg/kg/day to a maximum 60 mg/day (pediatrics), having no pathogenic mutations at the sequencing analysis for the known genes associated with NS (see appendix Table 1 for the full list of genes); Note: patients with biopsy-proven MCD/MesGN/FSGS recurrence in the kidney graft after renal transplantation with clinical features NS will be also considered.
• SRNS due to mutations in podocyte genes consisting in persistent nephrotic-range proteinuria (no complete/partial remission) despite prednisone 1 mg/kg/day or 2 mg/kg every other day for \> 4 months (adults) or despite prednisone 60 mg/m2/day or 2 mg/kg/day to a maximum 60 mg/day (pediatrics), harbouring pathogenic mutations at the sequencing analysis for genes associated with NS (see appendix Table 1for the full list of genes). This last condition will not consider possible treatments for the enrolment, as the patients usually are not treated with anti-CD20 monoclonal antibodies.
• For adults: written informed consent according to the guidelines of the Declaration of Helsinki.
• For children: written informed consent (according to the guidelines of the Declaration of Helsinki) of parent(s) or guardian.
• Healthy volunteers Healthy subjects (\>18 years) not known to suffer of any significant illness, not assuming any medication or drug on a regular basis, and whose mental state is such that they are able to understand and give valid consent to the study will be recruited among researchers and personnel of the IRCSS - Mario Negri Institute for Pharmacological Research. Only healthy subjects with negative urine analysis (urine dipstick, multistick will be considered for this study.

You may not qualify if:

• Reasonable possibility of a secondary cause of NS: active hepatitis B or C infection, or other chronic systemic infections; malignancy; drug abuse.
• Legal incapacity, intellectual disability/mental retardation, dementia, uncooperative attitude or any other evidence that patient will not be able to understand the study procedures and aims and to give written informed consent.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"

Ranica, BG, 24020, Italy

Location

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Giuseppe Remuzzi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 3, 2023
• Study Start: April 2, 2019
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)