<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03016455</url>
  </required_header>
  <id_info>
    <org_study_id>BHL (RB 12.047)</org_study_id>
    <nct_id>NCT03016455</nct_id>
  </id_info>
  <brief_title>B Cell Lymphocyte in Humoral Rejection and Alloimmunisation</brief_title>
  <acronym>BHL</acronym>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Brest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Brest</source>
  <brief_summary>
    <textblock>
      This study aims to better characterise B cell phenotype and functional abnormalities in&#xD;
      kidney transplant patients producing donor specific antibody (DSA) and in those with chronic&#xD;
      antibody mediated rejection (cAMR) and to search for a predictive tool (biomarker). The&#xD;
      functional analysis will help to better understand B cell-dependant mechanisms implied in T&#xD;
      cell proliferation and better target future treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The principal objective is to better understand the B cell dependant mechanisms of the&#xD;
      chronic antibody mediated rejection (cAMR). A particular focus will be done on the mechanisms&#xD;
      that could explain the natural history of chronic humoral mediated rejection and of pathways&#xD;
      from DSA negative status toward DSA positive status and from DSA positive status to&#xD;
      histological lesions. The following will be undergone for three categories of patients&#xD;
      (stable patients, DSA positive patients without cAMR and DSA positive patients with cAMR) :&#xD;
&#xD;
        -  A phenotypic analysis of B cells of patients suffering from chronic humoral rejection or&#xD;
           who are simply DSA positive.&#xD;
&#xD;
        -  A functional analysis in autologous cultures in order to confirm our preliminary&#xD;
           results.&#xD;
&#xD;
        -  A functional analysis in a heterologous proliferation test aiming at a better&#xD;
           understanding of the absence of B cell regulation of T cell proliferation in patients&#xD;
           suffering from cAMR.&#xD;
&#xD;
        -  A cytokine analysis (IL10, alpha-tumor necrosis factor, gamma-interferon dosing), for a&#xD;
           better understanding of the mechanisms that are involved in the regulation of the T cell&#xD;
           response that is induced by the B cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>June 2013</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of the ratio (percentage and absolute values) of mature LB subpopulations (LBm1 to LBm5) and of memory LB by specific labellings</measure>
    <time_frame>At the inclusion day</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells</measure>
    <time_frame>At the inclusion day</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of the proliferation of T cells in a heterologous test</measure>
    <time_frame>At the inclusion day</time_frame>
    <description>aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing)</measure>
    <time_frame>At the inclusion day</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between phenotypic and functional evaluations, and clinical outcome</measure>
    <time_frame>One year post inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison of the B cell subpopulations before and after rituximab treatment</measure>
    <time_frame>One year post inclusion</time_frame>
    <description>In a subgroup of patients, the ones that will happen to be treated by rituximab for a rejection episode.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">125</enrollment>
  <condition>Renal Transplant</condition>
  <arm_group>
    <arm_group_label>DSA positive patients without cAMR</arm_group_label>
    <description>Presence of DSA w/o cAMR</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DSA positive patients with cAMR</arm_group_label>
    <description>Presence of DSA w/ cAMR</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stable patients</arm_group_label>
    <description>No DSA No cAMR</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Presence of DSA w/ cAMR</intervention_name>
    <arm_group_label>DSA positive patients with cAMR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Presence of DSA w/o cAMR</intervention_name>
    <arm_group_label>DSA positive patients without cAMR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No DSA No cAMR</intervention_name>
    <arm_group_label>Stable patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole Blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        100 kidney graft recipients with DSA or cAMR (renal dysfunction, positive DSA, allograft&#xD;
        nephropathy), and 25 stable patients of 13 French transplantation centres.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Non stable patients :&#xD;
&#xD;
               -  Patient older than 18 years old.&#xD;
&#xD;
               -  Patient which is the recipient of a renal transplant&#xD;
&#xD;
               -  Patient who develops anti donor antibodies after the transplantation and / or&#xD;
                  suffering from a histologically-proven antibody mediated rejection.&#xD;
&#xD;
               -  Patient who has signed an informed consent form&#xD;
&#xD;
          -  Stable patients :&#xD;
&#xD;
               -  Patient older than 18 years old.&#xD;
&#xD;
               -  Patient that is the recipient of a renal transplant for more than one year&#xD;
&#xD;
               -  Patient who has accepted to participate in the Brest Kidney graft recipient&#xD;
                  collection&#xD;
&#xD;
               -  Patient that is not suffering from any rejection, that has a good renal function&#xD;
                  and a low proteinuria&#xD;
&#xD;
               -  Patient that has not developed any DSA.&#xD;
&#xD;
        Exclusion criteria :&#xD;
&#xD;
        - Patients that has not signed the consent form.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yannick LE MEUR, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital, Brest</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yannick LE MEUR, MD PhD</last_name>
    <email>yannick.lemeur@chu-brest.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU Amiens</name>
      <address>
        <city>Amiens</city>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Chu Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Brest</name>
      <address>
        <city>Brest</city>
        <zip>29200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yannick LE MEUR, MD PhD</last_name>
      <email>yannick.lemeur@chu-brest.fr</email>
    </contact>
    <investigator>
      <last_name>Yannick LE MEUR, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU CAEN</name>
      <address>
        <city>Caen</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Chu Clermont Ferrand</name>
      <address>
        <city>Clermont Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>APHP Hôpital Necker</name>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Reims</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Rouen</name>
      <address>
        <city>Rouen</city>
        <zip>76230</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Hôpitaux Universitaires de Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>CHU Tours</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>August 30, 2016</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>May 2, 2017</last_update_submitted>
  <last_update_submitted_qc>May 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Kidney Transplant</keyword>
  <keyword>Immunology</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03016455
org study id: BHL (RB 12.047)
nct id: NCT03016455
lead sponsor: 
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.
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.
observational model: Case-Control
time perspective: Prospective
measure: 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
measure: Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells
time frame: At the inclusion day
measure: Evaluation of the proliferation of T cells in a heterologous test
time frame: At the inclusion day
description: aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR
measure: cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing)
time frame: At the inclusion day
description: 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.
measure: Correlation between phenotypic and functional evaluations, and clinical outcome
time frame: One year post inclusion
measure: comparison of the B cell subpopulations before and after rituximab treatment
time frame: One year post inclusion
description: In a subgroup of patients, the ones that will happen to be treated by rituximab for a rejection episode.
arm group label: DSA positive patients without cAMR
description: Presence of DSA w/o cAMR
arm group label: DSA positive patients with cAMR
description: Presence of DSA w/ cAMR
arm group label: Stable patients
description: No DSA No cAMR
intervention type: Other
intervention name: Presence of DSA w/ cAMR
arm group label: DSA positive patients with cAMR
intervention type: Other
intervention name: Presence of DSA w/o cAMR
arm group label: DSA positive patients without cAMR
intervention type: Other
intervention name: No DSA No cAMR
arm group label: Stable patients
Whole Blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yannick LE MEUR, MD PhD
role: Study Director
affiliation: University Hospital, Brest
last name: Yannick LE MEUR, MD PhD
email: yannick.lemeur@chu-brest.fr
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
country: France
responsible party type: Sponsor