Immunopathological Analysis in a French National Cohort of Membranous Nephropathy (IHMN)
Primary Purpose
Membranous Nephropathy
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Blood sample
Sponsored by
About this trial
This is an interventional screening trial for Membranous Nephropathy
Eligibility Criteria
Inclusion Criteria:
- Age 18 years or more
- Biopsy on a native kidney consistent with MN and/or positivity for serum anti-PLA2R1 and/or anti-THSD7A antibodies
- Signed informed consent
Exclusion Criteria:
- Diagnosis error based on the kidney biopsy staining or on serology analyses for the positivity for anti-PLA2R1 and/or anti-THSD7A
- Patients unable to give an informed consent
- Patients withdrawing an informed consent
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Cohort
Arm Description
All patients included will have to be taken blood samples
Outcomes
Primary Outcome Measures
To determine the incidence of Membranous Nephropathy (MN) and its evolution
as either complete remission (UPCR < 0.3 g/g, serum albumin > 35 g/L, eGFR > 60 ml/min/1.73 m²) or partial remission (UPCR < 3.5 g/g and reduction of at least 50% from baseline, < 20% increase of serum creatinin from baseline) or persistent nephrotic syndrome (UPCR > 3.5 g/g, serum albumin < 30 g/L)
Secondary Outcome Measures
Determination of incidence of primary and secondary forms of MN
Identification of environmental factors associated with the onset of MN
Thanks to a specific questionnaire data on medical history, lifestyle, demography and profession will be collected
Medical history: prior diagnosis of any autoimmune disease, cancer, infection or other, infection in the month before the diagnosis of MN, thrombosis, drugs taken at the moment of diagnosis, allergies and type of symptomes
Emotional state: emotional state at diagnosis, stressful or destabilizing event in the year preceding diagnosis of MN
Description of the standard of care for patients with MN in France
Treatment names and their duration (in weeks) will be collected
the prognostic value of epitope spreading in patients with PLA2R1-associated MN
Epitope spreading status is determined by measuring the positivity to anti-CysR, anti-CTLD1 and CTLD7 antibodies in the serum, by the means of ELISA and expressed as RU/mL. The patients with antibodies targetting CysR only are considered as non-spreaders, while the patients additionnaly targetting either CTLD1 and/or CTLD7 are considered as spreaders. Epitope spreading status (non-spreader or spreader) will be correlated to clinical outcome (complete remission, partial remission or persistent nephrotic syndrome, as defined under primary outcome measures) one year after inclusion.
Characterization of HLA typing of MN patients
Isolation of DNA and genotyping will be performed with the use of standard procedures of Next Generation Sequencing
Prognostic value of tissue staining for glomerular deposit of PLA2R1, THSD7A, as welle as of different IgG subclasses
Positivity for PLA2R1, THSD7A and NELL-1 antigens will be determined using immunostaining with antibodies against PLA2R1, THSD7A and NELL-1, and Positivity for IgG1 IgG2, IgG3 and IgG4 subclasses will be determined using immunostaining with antibodies against IgG1 IgG2, IgG3 and IgG4, respectively, in glomeruli of kidney biopsy at inclusion. The positivity of tissue staining for PLA2R1, THSD7A and NELL-1or Ig subclasses will be correlated to the patient's clinical outcome one year after inclusion (complete remission, partial remission or persistent nephrotic syndrome, as defined under primary outcome measures).
Full Information
NCT ID
NCT04326218
First Posted
December 26, 2019
Last Updated
April 3, 2020
Sponsor
Centre Hospitalier Universitaire de Nice
1. Study Identification
Unique Protocol Identification Number
NCT04326218
Brief Title
Immunopathological Analysis in a French National Cohort of Membranous Nephropathy
Acronym
IHMN
Official Title
Immunopathological Analysis in a French National Cohort of Membranous Nephropathy (IHMN)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2020 (Anticipated)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
National cohort of all cases of membranous nephropathy (MN) during a 1 year period in France, based on a pathological and/or serological diagnostic, collecting the data on:
incidence of MN
prevalence of anti-PLA2R1 and anti-THSD7A
clinical outcome one year after diagnosis or after relapse (complete remission, partial remission or persistent nephrotic syndrome)
environmental risk factors for the onset of MN
HLA markers
patient care status in France
Detailed Description
Membranous nephropathy is a rare auto-immune disease, yet a major cause of nephrotic syndrome in adults. It is characterised by the deposition of antigen-antibody complexes on the glomerular basement membrane, leading to a decreased filtration rate and eventually kidney failure. About one third of cases have a favourable outcome without any treatment, another third requires a long term symptomatic treatment to manage their symptoms, and the last third of patients advances to end stage renal failure, requiring dialysis and kidney graft. MN can be associated with cancer, infections, other auto-immune diseases and with certain drugs (secondary MN), but most often it is idiopathic. In the latter form two antigens have been identified, PLA2R1 and THSD7A, with corresponding auto-antibodies in 70% and 2% of MN patients, respectively. GWAS studies identified several alleles associated with a higher risk of developing MN, however, since these are common variants they cannot explain the onset of MN in the vast majority of cases. Since MN is a rare disease, the number of new cases per each center is low, and nation-wide studies are needed to correctly evaluate its incidence and risk factors for the onset of MN, as well as validate previously published findings in monocentric studies on the prognostic value of PLA2R1 epitope spreading (immunisation against multiple domains of PLA2R1).
This study aims to establish a French national cohort of all cases of MN in a one year period in France. The inclusion will last one year with one additional year of follow-up, for a total of 2 years. In the first year, nephrologists of each associate centers in France will propose the study to each of their patients diagnosed with MN. In addition, clinical information will be collected, as well as a survey on patients' lifestyle habits. Serum samples will be sent for centralised analyses in Nice.
This study will help to clarify the results from single center studies, such as the prognostic value of epitope spreading. The information acquired on environmental risk factors will help us understand the pathophysiological mechanisms leading to the onset of MN et, by association, to other auto-immune diseases. With this knowledge, measures could be put in place to protect the population at risk.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranous Nephropathy
7. Study Design
Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Descriptive analysis of patient cohort who will be subjected to specific samples related to the study
Masking
None (Open Label)
Allocation
N/A
Enrollment
400 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort
Arm Type
Other
Arm Description
All patients included will have to be taken blood samples
Intervention Type
Other
Intervention Name(s)
Blood sample
Intervention Description
Serum samples will be sent for centralised analyses in Nice.
On these samples, different analysis will be performed :
anti-PLA2R1 and anti-THSD7A antibodies
anti-PLA2R1 and anti-THSD7A epitopes
HLA typing
Primary Outcome Measure Information:
Title
To determine the incidence of Membranous Nephropathy (MN) and its evolution
Description
as either complete remission (UPCR < 0.3 g/g, serum albumin > 35 g/L, eGFR > 60 ml/min/1.73 m²) or partial remission (UPCR < 3.5 g/g and reduction of at least 50% from baseline, < 20% increase of serum creatinin from baseline) or persistent nephrotic syndrome (UPCR > 3.5 g/g, serum albumin < 30 g/L)
Time Frame
one year after inclusion
Secondary Outcome Measure Information:
Title
Determination of incidence of primary and secondary forms of MN
Time Frame
24 months
Title
Identification of environmental factors associated with the onset of MN
Description
Thanks to a specific questionnaire data on medical history, lifestyle, demography and profession will be collected
Medical history: prior diagnosis of any autoimmune disease, cancer, infection or other, infection in the month before the diagnosis of MN, thrombosis, drugs taken at the moment of diagnosis, allergies and type of symptomes
Emotional state: emotional state at diagnosis, stressful or destabilizing event in the year preceding diagnosis of MN
Time Frame
24 months
Title
Description of the standard of care for patients with MN in France
Description
Treatment names and their duration (in weeks) will be collected
Time Frame
24 months
Title
the prognostic value of epitope spreading in patients with PLA2R1-associated MN
Description
Epitope spreading status is determined by measuring the positivity to anti-CysR, anti-CTLD1 and CTLD7 antibodies in the serum, by the means of ELISA and expressed as RU/mL. The patients with antibodies targetting CysR only are considered as non-spreaders, while the patients additionnaly targetting either CTLD1 and/or CTLD7 are considered as spreaders. Epitope spreading status (non-spreader or spreader) will be correlated to clinical outcome (complete remission, partial remission or persistent nephrotic syndrome, as defined under primary outcome measures) one year after inclusion.
Time Frame
24 months
Title
Characterization of HLA typing of MN patients
Description
Isolation of DNA and genotyping will be performed with the use of standard procedures of Next Generation Sequencing
Time Frame
12 months
Title
Prognostic value of tissue staining for glomerular deposit of PLA2R1, THSD7A, as welle as of different IgG subclasses
Description
Positivity for PLA2R1, THSD7A and NELL-1 antigens will be determined using immunostaining with antibodies against PLA2R1, THSD7A and NELL-1, and Positivity for IgG1 IgG2, IgG3 and IgG4 subclasses will be determined using immunostaining with antibodies against IgG1 IgG2, IgG3 and IgG4, respectively, in glomeruli of kidney biopsy at inclusion. The positivity of tissue staining for PLA2R1, THSD7A and NELL-1or Ig subclasses will be correlated to the patient's clinical outcome one year after inclusion (complete remission, partial remission or persistent nephrotic syndrome, as defined under primary outcome measures).
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years or more
Biopsy on a native kidney consistent with MN and/or positivity for serum anti-PLA2R1 and/or anti-THSD7A antibodies
Signed informed consent
Exclusion Criteria:
Diagnosis error based on the kidney biopsy staining or on serology analyses for the positivity for anti-PLA2R1 and/or anti-THSD7A
Patients unable to give an informed consent
Patients withdrawing an informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara SEITZ-POLSKI, MD
Phone
+33 4 92 03 55 02
Email
seitz-polski.b@chu-nice.fr
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No data will be shared
Citations:
PubMed Identifier
36283759
Citation
Cremoni M, Agbekodo S, Teisseyre M, Zorzi K, Brglez V, Benzaken S, Esnault V, Planchard JH, Seitz-Polski B. Toxic Occupational Exposures and Membranous Nephropathy. Clin J Am Soc Nephrol. 2022 Nov;17(11):1609-1619. doi: 10.2215/CJN.02930322. Epub 2022 Oct 25.
Results Reference
derived
Learn more about this trial
Immunopathological Analysis in a French National Cohort of Membranous Nephropathy
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