<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/NCT03755297</url>
  </required_header>
  <id_info>
    <org_study_id>5601</org_study_id>
    <nct_id>NCT03755297</nct_id>
  </id_info>
  <brief_title>Effect of the Inhibitors of the Way JAK-STAT on Regulatory B Cells</brief_title>
  <acronym>JAK-INH2</acronym>
  <official_title>Effect of the Inhibitors of the Way JAK-STAT on Regulatory B Cells in the Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centre National de la Recherche Scientifique, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate whether inhibitors of the JAK / STAT signaling pathway can&#xD;
      increase anti-inflammatory functions of B cells in patients with RA using in vitro and in&#xD;
      vivo experiments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will first analyze the effect of inhibitors of the JAK / STAT pathway in vitro on&#xD;
      B-cell phenotypes and functions in 30 RA patients and 30 patients with osteoarthritis. It&#xD;
      will also study the phenotypes and functions of B cells in RA patients for whom JAK / STAT&#xD;
      inhibitor treatment has been prescribed by the patient's usual rheumatologist. The analysis&#xD;
      will be done before the start of treatment and 3 months later. The phenotypes of B-cells will&#xD;
      be assessed by flow cytometry with intra- and extra-cellular stainings. The functions of B&#xD;
      cells will be assessed by their ability to differenciate naïve T cells in coculture.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Default of recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Actual">November 12, 2022</completion_date>
  <primary_completion_date type="Actual">August 12, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of regulatory B cells induced by JAKi in vitro</measure>
    <time_frame>4 months</time_frame>
    <description>IL-10+ CD19+ cells after in vitro exposure of JAKi</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of regulatory T cells induced by JAKi treated B cells in vitro</measure>
    <time_frame>4 months</time_frame>
    <description>CD25hiCD126lo/-CD4+ after 3 days of coculture with JAKi pretreated B cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Th1 induced by JAKi treated B cells in vitro</measure>
    <time_frame>4 months</time_frame>
    <description>Interferon gamma+CD4+ after 3 days of coculture with JAKi pretreated B cells</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Rheumatoid arthritis</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients responding to ACR/EULAR 2010 criteria and Blood sample analysis of patients treated as standard care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Osteoarthritis</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Control patients and Blood sample analysis of patients treated as standard care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rheumatoid arthritis with JAK/STAT inhibitors</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Standard use of JAK/STAT inhibitors and Blood sample analysis of patients treated as standard care</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood sample analysis of patients treated as standard care</intervention_name>
    <description>Blood sample to analyse percentage of blood cells (regulatory B cells et T cells)</description>
    <arm_group_label>Osteoarthritis</arm_group_label>
    <arm_group_label>Rheumatoid arthritis</arm_group_label>
    <arm_group_label>Rheumatoid arthritis with JAK/STAT inhibitors</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  General criteria&#xD;
&#xD;
          -  Patient, of 18 and more years old&#xD;
&#xD;
          -  Subject affiliated to a social security system&#xD;
&#xD;
          -  Subject not being in period of exclusion with regard to another protocol&#xD;
&#xD;
          -  Absence of pregnancy in the inclusion (date of the last period, use of a contraceptive&#xD;
             method, ß -HCG impulsive person in case of doubt)&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Criteria of inclusion of the group rheumatoid arthritis (in vitro studies):&#xD;
&#xD;
          -  Rheumatoid arthritis, corresponding to the the classification ACR / EULAR 2010&#xD;
             criteria&#xD;
&#xD;
          -  Criteria of inclusion of the group arthritis (in vitro studies):&#xD;
&#xD;
          -  Spinal degenerative osteoarthritis or degenerative osteoarthritis of the members,&#xD;
             according to the clinical and radiological elements.&#xD;
&#xD;
          -  Criteria of inclusion of the group rheumatoid arthritis, longitudinal study at the&#xD;
             patients treated by JAK / STAT inhibitors :&#xD;
&#xD;
          -  Rheumatoid Polyarthritis, corresponding to the classification ACR / EULAR 2010&#xD;
             criteria&#xD;
&#xD;
          -  Patient to whom a treatment by inhibitor of the way JAK / STAT was proposed in current&#xD;
             care of rheumatoid arthritis.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  General criteria&#xD;
&#xD;
          -  Corticosteroid therapy superior to 10 mg / j&#xD;
&#xD;
          -  Drip of corticoids in the previous month&#xD;
&#xD;
          -  Pregnant or breast-feeding Patients&#xD;
&#xD;
          -  Patient under protection(saving) of justice&#xD;
&#xD;
          -  Under guardianship Patient or guardianship&#xD;
&#xD;
          -  Current Infection&#xD;
&#xD;
          -  Criteria of non-inclusion of the group rheumatoid polyarthritis ( in vitro studies):&#xD;
&#xD;
          -  Treatment by immunomodulateur or biotherapics (anti-TNF alpha, tocilizumab, abatacept&#xD;
             or rituximab) in the previous year&#xD;
&#xD;
          -  Criteria of non-inclusion of the group arthritis ( in vitro studies):&#xD;
&#xD;
          -  History of autoimmune disease or néoplasie&#xD;
&#xD;
          -  Treatment by immunomodulateur or biotherapics (anti-TNF alpha, tocilizumab, abatacept&#xD;
             or rituximab)&#xD;
&#xD;
          -  Criteria of non-inclusion of the group rheumatoid arthritis, longitudinal study at the&#xD;
             patients treated by JAK / STAT inhibitors :&#xD;
&#xD;
        Treatment by rituximab in the previous year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claire DAIEN, PH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>September 13, 2023</last_update_submitted>
  <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid arthritis</keyword>
  <keyword>Regulatory B cells</keyword>
  <keyword>JAK/STAT inhibitors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03755297
org study id: 5601
nct id: NCT03755297
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will investigate whether inhibitors of the JAK / STAT signaling pathway can
      increase anti-inflammatory functions of B cells in patients with RA using in vitro and in
      vivo experiments.
This study will first analyze the effect of inhibitors of the JAK / STAT pathway in vitro on
      B-cell phenotypes and functions in 30 RA patients and 30 patients with osteoarthritis. It
      will also study the phenotypes and functions of B cells in RA patients for whom JAK / STAT
      inhibitor treatment has been prescribed by the patient's usual rheumatologist. The analysis
      will be done before the start of treatment and 3 months later. The phenotypes of B-cells will
      be assessed by flow cytometry with intra- and extra-cellular stainings. The functions of B
      cells will be assessed by their ability to differenciate naïve T cells in coculture.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Percentage of regulatory B cells induced by JAKi in vitro
time frame: 4 months
description: IL-10+ CD19+ cells after in vitro exposure of JAKi
measure: Percentage of regulatory T cells induced by JAKi treated B cells in vitro
time frame: 4 months
description: CD25hiCD126lo/-CD4+ after 3 days of coculture with JAKi pretreated B cells
measure: Percentage of Th1 induced by JAKi treated B cells in vitro
time frame: 4 months
description: Interferon gamma+CD4+ after 3 days of coculture with JAKi pretreated B cells
arm group label: Rheumatoid arthritis
arm group type: Other
description: Patients responding to ACR/EULAR 2010 criteria and Blood sample analysis of patients treated as standard care
arm group label: Osteoarthritis
arm group type: Other
description: Control patients and Blood sample analysis of patients treated as standard care
arm group label: Rheumatoid arthritis with JAK/STAT inhibitors
arm group type: Other
description: Standard use of JAK/STAT inhibitors and Blood sample analysis of patients treated as standard care
intervention type: Other
intervention name: Blood sample analysis of patients treated as standard care
description: Blood sample to analyse percentage of blood cells (regulatory B cells et T cells)
arm group label: Osteoarthritis
arm group label: Rheumatoid arthritis
arm group label: Rheumatoid arthritis with JAK/STAT inhibitors
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Claire DAIEN, PH
role: Principal Investigator
affiliation: University Hospital, Montpellier
facility: 
country: France
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
sharing ipd: No