- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04095156
Autoreactive B Cells in Membranous Nephropathy (PEPTIDE)
November 2, 2022 updated by: Mario Negri Institute for Pharmacological Research
PLA2R Autoreactive B-Cell Subsets and Immune Cell Monitoring in Membranous Nephropathy: Identification of Outcome Predictors and Novel Insights Into Disease Pathogenesis
Membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome (NS) in adults.
The majority of MN patients show detectable circulating antibodies against the M-type phospholipase A2 receptor (PLA2R).
Infusion of anti-CD20 monoclonal antibodies results in a profound depletion of B-cells, which are thought to be responsible for anti-PLA2R production.
B-cell depletion is followed by NS remission in 70% of cases.
Limited evidence highlighted that differences in the B- and T-cell compartments may exist between responders and non-responders.
Owing to the non-homogenous efficacy of anti-CD20 treatment, investigators hypothesize that in MN patients who experience NS remission after B-cell depleting therapy, autoreactive B-cells may be mostly circulating, whereas in patients who do not respond to the same treatment, autoreactive B-cells may chiefly reside into secondary lymphoid organs - and thus be more resistant to the drug action.
Researchers will therefore extensively analyze the circulating immune repertoire of MN patients before and after the infusion of B-cell lineage depleting agents, assessing the presence of circulating PLA2R autoreactive B cells from appropriately stratified responder and non-responder patients.
Patients and healthy controls will be enrolled in this study.
Patients will be stratified according to gender, anti-PLA2R status, type of B-cell lineage depleting agent received and response to treatment.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Observational
Enrollment (Anticipated)
86
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Manuel Podestà, MD
- Phone Number: 003903545351
- Email: manuel.podesta@guest.marionegri.it
Study Locations
-
-
BG
-
Ranica, BG, Italy, 24020
- Recruiting
- Centro di Ricerche Cliniche per le Malattie Rare " Aldo e Cele Daccò"
-
Contact:
- Manuel Podesta, MD
- Phone Number: 0039 035 45351
- Email: Manuel.podesta@guest.marionegri.it
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Patients with biopsy-proven idiopathic MN, who are candidate to receive (prospective cohort) or who already received (retrospective cohort) a B-cell depleting treatment as per center clinical practice and healthy volunteers as controls
Description
Inclusion Criteria:
Patients inclusion criteria
- Males and females.
- Adults (> 18 years old).
- Patients with biopsy-proven idiopathic MN, who are candidate to receive (prospective cohort) or who already received (retrospective cohort) a B-cell depleting treatment as per center clinical practice.
- Mental state is such that they are able to understand and give valid consent to the study;
- Written informed consent according to the guidelines of the Declaration of Helsinki.
Healthy volunteers inclusion criteria
- Male and female (>18 years) not known to suffer of any significant illness;
- Not assuming any medication or drug on a regular basis;
- Negative urine analysis (urine dipstick, multistick);
- Written informed consent according to the guidelines of the Declaration of Helsinki
Exclusion Criteria:
Patients exclusion criteria
- Reasonable possibility of a secondary cause of MN (e.g.systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine).
- 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.
Healthy volunteers exclusion criteria
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Other
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Prospective cohort
Patients with biopsy-proven idiopathic MN, who are candidate to receive a B-cell depleting treatment as per center clinical practice.
|
Biochemical and flow-cytometry analysis of specimen collected.
|
Retrospective cohort
Patients with biopsy-proven idiopathic MN, who already received a B-cell depleting treatment as per center clinical practice.
|
Biochemical and flow-cytometry analysis of specimen collected.
|
Healthy volunteers cohort
Subjects > 18 years not known to suffer of any significant illness, not assuming any medication or drug on a regular basis.
|
Biochemical and flow-cytometry analysis of specimen collected.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in the frequency of anti-PLA2R autoreactive circulating B-cells.
Time Frame: Changes from baseline and 3,6,9,12 and 24 month.
|
Changes from baseline and 3,6,9,12 and 24 month.
|
Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in the frequency of immunoglobulin- and cytokine-secreting circulating B-cell subsets in resting and stimulated conditions.
Time Frame: Changes from baseline and 3,6,9,12 and 24 month.
|
Changes from baseline and 3,6,9,12 and 24 month.
|
Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in spontaneous / stimulated immunoglobulin (including anti-PLA2R) and cytokine release from circulating B-cell subpopulations.
Time Frame: Changes from baseline and 3,6,9,12 and 24 month.
|
Changes from baseline and 3,6,9,12 and 24 month.
|
Differences between MN patients and healthy controls, and between responders and non-responders in the frequency of circulating B-cell subpopulations.
Time Frame: Changes from baseline and 3,6,9,12 and 24 month.
|
Changes from baseline and 3,6,9,12 and 24 month.
|
Differences between MN patients and healthy controls, and between responders and non-responders in the frequency of circulating T-cell, NK-cell, monocyte and dendritic cell subpopulations.
Time Frame: Changes from baseline and 3,6,9,12 and 24 month.
|
Changes from baseline and 3,6,9,12 and 24 month.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 12, 2019
Primary Completion (Anticipated)
December 1, 2023
Study Completion (Anticipated)
December 1, 2023
Study Registration Dates
First Submitted
September 17, 2019
First Submitted That Met QC Criteria
September 18, 2019
First Posted (Actual)
September 19, 2019
Study Record Updates
Last Update Posted (Actual)
November 3, 2022
Last Update Submitted That Met QC Criteria
November 2, 2022
Last Verified
November 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PEPTIDE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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