Extramembranous GlomerulopathyBIOGEMNCT05428605
In Vitro Immunomodulation in Membranous Nephropathy Relapses
A study testing Blood sample in people with Extramembranous Glomerulopathy, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial summary
In order to propose the best therapeutic option to relapsed MN patients with strong activation of the Th17 pathway, the investigators propose to study in vitro the effect of different immunomodulators on the Th17/Treg balance, assessed by cytokine profile and lymphocyte phenotyping using flow cytometry. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extramembranous Glomerulopathy
- What is being tested?
- Blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 23 May 2022to 6 Jun 2025
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Patient with MN proven on renal biopsy or by the presence of anti-PLA2R1 or anti-THDS71 antibodies
- Relapsed MN, defined as proteinuria > 3.5g/g after achieving remission (partial or complete, definitions according to KDIGO 2012 guidelines)
- At a distance from any immunosuppressive treatment (at least 6 months)
- Freely given informed consent signed by the patient after clear, fair and appropriate information
- Affiliated to a social security system
Who cannot join
- Pregnant or breastfeeding woman
- Patient under 18 years of age
- Persons of legal age
Trial locations and contacts
1 site in 1 country.
About this study
Official title: In Vitro Study of the Efficacy of Different Immunomodulators on the Th17/Treg Balance in a Cohort of Relapsed Membranous Nephropathy
In order to propose the best therapeutic option to relapsed MN patients with strong activation of the Th17 pathway, the investigators propose to study in vitro the effect of different immunomodulators on the Th17/Treg balance, assessed by cytokine profile and lymphocyte phenotyping using flow cytometry.
Read the detailed description
Membranous Nephropathy (MN) is a rare autoimmune renal disease and the first cause of nephrotic syndrome in adults. In one third of cases, it progresses to end-stage renal failure. Rituximab has shown very good efficacy (60-80%) and excellent safety in this indication. However, one third of MN patients relapse after a course of rituximab, raising the question of maintenance treatment or repeated courses of rituximab whose long-term impact is unknown.
The investigators studied the cytokine profile of MN patients and demonstrated, after non-specific stimulation of innate immunity cells and T cells, a Th17 profile (increased levels of interleukin-6 (Il-6) and interleukin-17A (Il-17A) compared to healthy subjects), and inhibition of the Th1 (decreased IL-12p70 and Interferon-γ (IFN-γ)) and T regulatory T reg pathways (decreased IL-10) (doi: 10. 3389/fimmu.2020.574997).
Th17 cells and Treg cells with interconnected development have opposite roles. Th17 cells induce inflammation to initiate a reaction against a pathogen, while Treg cells control an inflammatory reaction.
The investigators showed that high Il-17A levels were associated with a risk of thrombotic events (p = 0.03) and relapse (p = 0.0006). A patient with an IL-17A level > 73 pg/ml had a 10.5-fold increased risk of relapse.
Rituximab-induced remission leads to an increase in Treg and Th1 pathway cytokines but has no impact on IL-17A production, which remains important even in remission.
Thus, in this group of patients with high IL-17A levels, targeted action on B lymphocytes is probably not sufficient to avoid relapse and the addition of a treatment aimed at inhibiting the Th17 pathway and promoting Treg induction seems legitimate.
Various potential treatment exist: anti-Il-6 antibodies (tocilizumab), anti-Il-17 antibodies (secukinumab), low-dose Il-2 (a few studies have demonstrated its ability to induce Treg in various autoimmune diseases), hydroxychloroquine in low doses (used in lupus to limit relapses and having an anti-inflammatory effect), the plant extract Alphanosos (anti-Th1) or Levamizole (validated in nephrotic syndrome in children).
In order to propose the best therapeutic option to relapsed MN patients with a strong activation of the Th17 pathway, the investigators propose to study in vitro the effect of these different immunomodulators on the Th17/Treg balance evaluated by cytokine profile and lymphocyte phenotyping in flow cytometry.
- Conditions
- Extramembranous Glomerulopathy
- Being tested
- Blood sample
- Keywords
- membranous nephropathy, immunomodulation, relapse, Th17/Treg pathways
- Medical subject headings
- Glomerulonephritis, Membranous, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleOther
10 mL on lithium heparinate tubes, 10 mL on EDTA tubes.
| Study group | Role | What they receive |
|---|---|---|
| GEM patients | Experimental | Not described Receives: Other: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine ELISA profiles of the Th17 pathway (IL-17 level), the Treg pathway (IL-10 level), the Th1 pathway (IL-12p70, IFN-γ) and the Th2 pathway (IL-4 and IL-5)
All cytokines (IL-17, IL-10, IL-12p70, IFN-γ, IL-4 and IL-5) measured by ELISA will be expressed in pg/ml.
Measured: 18 months
Secondary outcomes (1)
Lymphocyte phenotyping (Treg and Th17) determined by flow cytometry
Percentage of cells expressing the fluorescent marker of interest
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2022
- Study start23 May 2022
- Primary completion30 May 2024
- Study completion6 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Extramembranous GlomerulopathyStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- To compare in vitro the effect of different immunomodulators on Th17/Treg lymphocyte balance in a cohort of relapsed MN patients to determine the best therapeutic approach.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05428605
- Sponsor's protocol ID
- 20-AOIP-06
- Acronym
- BIOGEM
- Status last verified
- Mar 2026
- First submitted
- 10 Jun 2022
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD is not planned to be shared with other researchers than the investigators
Publications
Levraut M, Marignier R, Cohen M, Benoit J, Landes-Chateau C, Maillart E, Cremoni M, Seitz-Polski B, Pinto AL, Dumez P, Honnorat J, Lebrun-Frenay C. Relevance of Kappa and Lambda Free Light Chains in Autoimmune Astrocytopathy Associated With Anti-GFAP Antibodies. Ann Clin Transl Neurol. 2025 Sep;12(9):1785-1793. doi: 10.1002/acn3.70103. Epub 2025 Jun 28.
PubMed 40581835
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vitro Study of the Efficacy of Different Immunomodulators on the Th17/Treg Balance in a Cohort of Relapsed Membranous Nephropathy
- ClinicalTrials.gov ID
- NCT05428605
- Acronym / sponsor ID
- BIOGEM / 20-AOIP-06
- Conditions
- Extramembranous Glomerulopathy
- Keywords
- membranous nephropathy, immunomodulation, relapse, Th17/Treg pathways
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 23 May 2022 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 6 Jun 2025 (actual)
- First posted
- 23 Jun 2022 (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.
In order to propose the best therapeutic option to relapsed MN patients with strong activation of the Th17 pathway, the investigators propose to study in vitro the effect of different immunomodulators on the Th17/Treg balance, assessed by cytokine profile and lymphocyte phenotyping using flow cytometry.
Detailed description
Membranous Nephropathy (MN) is a rare autoimmune renal disease and the first cause of nephrotic syndrome in adults. In one third of cases, it progresses to end-stage renal failure. Rituximab has shown very good efficacy (60-80%) and excellent safety in this indication. However, one third of MN patients relapse after a course of rituximab, raising the question of maintenance treatment or repeated courses of rituximab whose long-term impact is unknown.
The investigators studied the cytokine profile of MN patients and demonstrated, after non-specific stimulation of innate immunity cells and T cells, a Th17 profile (increased levels of interleukin-6 (Il-6) and interleukin-17A (Il-17A) compared to healthy subjects), and inhibition of the Th1 (decreased IL-12p70 and Interferon-γ (IFN-γ)) and T regulatory T reg pathways (decreased IL-10) (doi: 10. 3389/fimmu.2020.574997).
Th17 cells and Treg cells with interconnected development have opposite roles. Th17 cells induce inflammation to initiate a reaction against a pathogen, while Treg cells control an inflammatory reaction.
The investigators showed that high Il-17A levels were associated with a risk of thrombotic events (p = 0.03) and relapse (p = 0.0006). A patient with an IL-17A level > 73 pg/ml had a 10.5-fold increased risk of relapse.
Rituximab-induced remission leads to an increase in Treg and Th1 pathway cytokines but has no impact on IL-17A production, which remains important even in remission.
Thus, in this group of patients with high IL-17A levels, targeted action on B lymphocytes is probably not sufficient to avoid relapse and the addition of a treatment aimed at inhibiting the Th17 pathway and promoting Treg induction seems legitimate.
Various potential treatment exist: anti-Il-6 antibodies (tocilizumab), anti-Il-17 antibodies (secukinumab), low-dose Il-2 (a few studies have demonstrated its ability to induce Treg in various autoimmune diseases), hydroxychloroquine in low doses (used in lupus to limit relapses and having an anti-inflammatory effect), the plant extract Alphanosos (anti-Th1) or Levamizole (validated in nephrotic syndrome in children).
In order to propose the best therapeutic option to relapsed MN patients with a strong activation of the Th17 pathway, the investigators propose to study in vitro the effect of these different immunomodulators on the Th17/Treg balance evaluated by cytokine profile and lymphocyte phenotyping in flow cytometry.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- To compare in vitro the effect of different immunomodulators on Th17/Treg lymphocyte balance in a cohort of relapsed MN patients to determine the best therapeutic approach.
| Arm | Type | Receives |
|---|---|---|
| GEM patients | Experimental | Other: Blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years
- Patient with MN proven on renal biopsy or by the presence of anti-PLA2R1 or anti-THDS71 antibodies
- Relapsed MN, defined as proteinuria > 3.5g/g after achieving remission (partial or complete, definitions according to KDIGO 2012 guidelines)
- At a distance from any immunosuppressive treatment (at least 6 months)
- Freely given informed consent signed by the patient after clear, fair and appropriate information
Key exclusion criteria (3 listed)
- Pregnant or breastfeeding woman
- Patient under 18 years of age
- Persons of legal age
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 sample10 mL on lithium heparinate tubes, 10 mL on EDTA tubes. | Other | GEM patients |
Primary outcome
Cytokine ELISA profiles of the Th17 pathway (IL-17 level), the Treg pathway (IL-10 level), the Th1 pathway (IL-12p70, IFN-γ) and the Th2 pathway (IL-4 and IL-5)
Time frame: 18 months
All cytokines (IL-17, IL-10, IL-12p70, IFN-γ, IL-4 and IL-5) measured by ELISA will be expressed in pg/ml.
1 secondary outcome
Lymphocyte phenotyping (Treg and Th17) determined by flow cytometry
Time frame: 18 months
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 24 Mar 2026.
- Results publication: PubMed 40581835Levraut M, Marignier R, Cohen M, Benoit J, Landes-Chateau C, Maillart E, Cremoni M, Seitz-Polski B, Pinto AL, Dumez P, Honnorat J, Lebrun-Frenay C. Relevance of Kappa and Lambda Free Light Chains in Autoimmune Astrocytopathy Associated With Anti-GFAP Antibodies. Ann Clin Transl Neurol. 2025 Sep;12(9):1785-1793. doi: 10.1002/acn3.70103. Epub 2025 Jun 28.
- Individual participant dataSharing planned: No. IPD is not planned to be shared with other researchers than the investigators
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 sample in people with Extramembranous Glomerulopathy, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
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 6 inclusion and 3 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 24 Mar 2026. 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 France. 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?
Cytokine ELISA profiles of the Th17 pathway (IL-17 level), the Treg pathway (IL-10 level), the Th1 pathway (IL-12p70, IFN-γ) and the Th2 pathway (IL-4 and IL-5) (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05428605, which also lists 1 linked publication.
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 24 Mar 2026.