B Cell Lymphocyte in Humoral Rejection and Alloimmunisation (BHL)

May 2, 2017 updated by: University Hospital, Brest
This study aims to better characterise B cell phenotype and functional abnormalities in kidney transplant patients producing donor specific antibody (DSA) and in those with chronic antibody mediated rejection (cAMR) and to search for a predictive tool (biomarker). The functional analysis will help to better understand B cell-dependant mechanisms implied in T cell proliferation and better target future treatments.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The principal objective is to better understand the B cell dependant mechanisms of the chronic antibody mediated rejection (cAMR). A particular focus will be done on the mechanisms that could explain the natural history of chronic humoral mediated rejection and of pathways from DSA negative status toward DSA positive status and from DSA positive status to histological lesions. The following will be undergone for three categories of patients (stable patients, DSA positive patients without cAMR and DSA positive patients with cAMR) :

  • A phenotypic analysis of B cells of patients suffering from chronic humoral rejection or who are simply DSA positive.
  • A functional analysis in autologous cultures in order to confirm our preliminary results.
  • A functional analysis in a heterologous proliferation test aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR.
  • A cytokine analysis (IL10, alpha-tumor necrosis factor, gamma-interferon dosing), for a better understanding of the mechanisms that are involved in the regulation of the T cell response that is induced by the B cells.

Study Type

Observational

Enrollment (Anticipated)

125

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
        • Completed
        • CHU Amiens
      • Angers, France, 49933
        • Completed
        • Chu Angers
      • Brest, France, 29200
        • Recruiting
        • CHU Brest
      • Caen, France, 14033
        • Completed
        • CHU Caen
      • Clermont Ferrand, France, 63003
        • Completed
        • CHU Clermont Ferrand
      • Limoges, France, 87042
        • Withdrawn
        • CHU Limoges
      • Paris, France, 75743
        • Completed
        • APHP Hôpital Necker
      • Poitiers, France, 86021
        • Completed
        • CHU Poitiers
      • Reims, France, 51092
        • Completed
        • CHU Reims
      • Rennes, France, 35033
        • Completed
        • Chu Rennes
      • Rouen, France, 76230
        • Completed
        • CHU Rouen
      • Strasbourg, France, 67091
        • Completed
        • Hôpitaux Universitaires de Strasbourg
      • Tours, France, 37044
        • Completed
        • CHU Tours

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

100 kidney graft recipients with DSA or cAMR (renal dysfunction, positive DSA, allograft nephropathy), and 25 stable patients of 13 French transplantation centres.

Description

Inclusion criteria :

  • Non stable patients :

    • Patient older than 18 years old.
    • Patient which is the recipient of a renal transplant
    • Patient who develops anti donor antibodies after the transplantation and / or suffering from a histologically-proven antibody mediated rejection.
    • Patient who has signed an informed consent form

  • Stable patients :

    • Patient older than 18 years old.
    • Patient that is the recipient of a renal transplant for more than one year
    • Patient who has accepted to participate in the Brest Kidney graft recipient collection
    • Patient that is not suffering from any rejection, that has a good renal function and a low proteinuria
    • Patient that has not developed any DSA.

Exclusion criteria :

- Patients that has not signed the consent form.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
DSA positive patients without cAMR
Presence of DSA w/o cAMR
Other: Presence of DSA w/o cAMR
DSA positive patients with cAMR
Presence of DSA w/ cAMR
Other: Presence of DSA w/ cAMR
Stable patients
No DSA No cAMR
Other: No DSA No cAMR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the ratio (percentage and absolute values) of mature LB subpopulations (LBm1 to LBm5) and of memory LB by specific labellings
Time Frame: At the inclusion day
At the inclusion day
Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells
Time Frame: At the inclusion day
At the inclusion day
Evaluation of the proliferation of T cells in a heterologous test
Time Frame: At the inclusion day
aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR
At the inclusion day
cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing)
Time Frame: At the inclusion day
for a better understanding of the mechanisms that are involved in the regulation of the T cell response that is induced by the B cells.
At the inclusion day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between phenotypic and functional evaluations, and clinical outcome
Time Frame: One year post inclusion
One year post inclusion
comparison of the B cell subpopulations before and after rituximab treatment
Time Frame: One year post inclusion
In a subgroup of patients, the ones that will happen to be treated by rituximab for a rejection episode.
One year post inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Brest

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

June 1, 2013

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

August 30, 2016

First Submitted That Met QC Criteria

January 9, 2017

First Posted (Estimate)

January 10, 2017

Study Record Updates

Last Update Posted (Actual)

May 4, 2017

Last Update Submitted That Met QC Criteria

May 2, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • BHL (RB 12.047)

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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