Nephrotic SyndromeBLADENCT05712369
B Cells in Idiopathic Nephrotic Syndrome
A study testing Blood sampling in people with Nephrotic Syndrome, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 years and olderHealthy volunteers can take part
- Conditions the study is for
- Nephrotic Syndrome
- What is being tested?
- Blood sampling
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteItaly
- Study dates
- 2 Apr 2019to 7 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"
Ranica, BG, 24020
About this study
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
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.
Read the 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.
- Conditions
- Nephrotic Syndrome
- Being tested
- Blood sampling
- Keywords
- Nephrotic syndrome, Steroids, B cells, B cells, Anti-CD20 antibodies
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Prospective cohort | Experimental | Patients with INS due to biopsy-proven MCD or FSGS or MesGN candidate to anti-CD20 monoclonal antibodies therapy. Receives: 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. Receives: 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. Receives: Other: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: At baseline, 6,9 12 and 24 months after treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2023
- Study start2 Apr 2019
- Primary completion7 Nov 2024
- Study completion7 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Remuzzi, MD, Study director, Istituto Di Ricerche Farmacologiche Mario Negri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05712369
- Sponsor's protocol ID
- BLADE
- Acronym
- BLADE
- Status last verified
- Nov 2024
- First submitted
- 25 Jan 2023
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05712369
- Acronym / sponsor ID
- BLADE / BLADE
- Conditions
- Nephrotic Syndrome
- Keywords
- Nephrotic syndrome, Steroids, B cells, B cells, Anti-CD20 antibodies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 2 Apr 2019 (actual)
- Primary completion
- 7 Nov 2024 (actual)
- Study completion
- 7 Nov 2024 (actual)
- First posted
- 3 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Prospective cohort | Experimental | Other: Blood samplingPatients with INS due to biopsy-proven MCD or FSGS or MesGN candidate to anti-CD20 monoclonal antibodies therapy. |
| Retrospective cohort | Experimental | Other: Blood samplingPatients with INS due to biopsy-proven MCD or FSGS or MesGN, treated with anti-CD20 monoclonal antibodies therapy. |
| Healthy volunteers cohort | Active comparator | Other: Blood samplingSubjects not known to suffer of any significant illness, not assuming any medication or drug on a regular basis. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Patients will be included irrespective of previous (retrospective cohort) or planned (prospective cohort) treatments 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplingBefore 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. | Other | Healthy volunteers cohort, Prospective cohort, Retrospective cohort |
Primary outcome
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At baseline, 6,9 12 and 24 months after treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Remuzzi, MD study director
Istituto Di Ricerche Farmacologiche Mario Negri
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sampling in people with Nephrotic Syndrome, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: At baseline, 6,9 12 and 24 months after treatment.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.