Ignite Creation Date:
2025-12-25 @ 3:29 AM
Ignite Modification Date:
2025-12-26 @ 2:10 AM
Study NCT ID:
NCT05428605
Status:
COMPLETED
Last Update Posted:
2025-12-03
First Post:
2022-06-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
In Vitro Immunomodulation in Membranous Nephropathy Relapses
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015433', 'term': 'Glomerulonephritis, Membranous'}, {'id': 'D012008', 'term': 'Recurrence'}], 'ancestors': [{'id': 'D005921', 'term': 'Glomerulonephritis'}, {'id': 'D009393', 'term': 'Nephritis'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-05-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2025-06-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-11-25', 'studyFirstSubmitDate': '2022-06-10', 'studyFirstSubmitQcDate': '2022-06-20', 'lastUpdatePostDateStruct': {'date': '2025-12-03', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2022-06-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-05-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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)', 'timeFrame': '18 months', 'description': 'All cytokines (IL-17, IL-10, IL-12p70, IFN-γ, IL-4 and IL-5) measured by ELISA will be expressed in pg/ml.'}], 'secondaryOutcomes': [{'measure': 'Lymphocyte phenotyping (Treg and Th17) determined by flow cytometry', 'timeFrame': '18 months', 'description': 'Percentage of cells expressing the fluorescent marker of interest'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['membranous nephropathy', 'immunomodulation', 'relapse', 'Th17/Treg pathways'], 'conditions': ['Extramembranous Glomerulopathy']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe 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).\n\nTh17 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.\n\nThe 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.\n\nRituximab-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.\n\nThus, 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.\n\nVarious 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).\n\nIn 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age ≥ 18 years\n2. Patient with MN proven on renal biopsy or by the presence of anti-PLA2R1 or anti-THDS71 antibodies\n3. Relapsed MN, defined as proteinuria \\> 3.5g/g after achieving remission (partial or complete, definitions according to KDIGO 2012 guidelines)\n4. At a distance from any immunosuppressive treatment (at least 6 months)\n5. Freely given informed consent signed by the patient after clear, fair and appropriate information\n6. Affiliated to a social security system\n\nExclusion Criteria:\n\n1. Pregnant or breastfeeding woman\n2. Patient under 18 years of age\n3. Persons of legal age'}, 'identificationModule': {'nctId': 'NCT05428605', 'acronym': 'BIOGEM', 'briefTitle': 'In Vitro Immunomodulation in Membranous Nephropathy Relapses', 'organization': {'class': 'OTHER', 'fullName': 'Centre Hospitalier Universitaire de Nice'}, 'officialTitle': 'In Vitro Study of the Efficacy of Different Immunomodulators on the Th17/Treg Balance in a Cohort of Relapsed Membranous Nephropathy', 'orgStudyIdInfo': {'id': '20-AOIP-06'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'GEM patients', 'interventionNames': ['Other: Blood sample']}], 'interventions': [{'name': 'Blood sample', 'type': 'OTHER', 'description': '10 mL on lithium heparinate tubes, 10 mL on EDTA tubes.', 'armGroupLabels': ['GEM patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '06200', 'city': 'Nice', 'country': 'France', 'facility': 'Centre Hospitalier Universitaire de Nice', 'geoPoint': {'lat': 43.70313, 'lon': 7.26608}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'IPD is not planned to be shared with other researchers than the investigators'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centre Hospitalier Universitaire de Nice', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}