<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/NCT03841318</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2018/53</org_study_id>
    <nct_id>NCT03841318</nct_id>
  </id_info>
  <brief_title>Involvement of Immune Cells Derived From the Intestine in Sjogren's Syndrome</brief_title>
  <acronym>SINGOU</acronym>
  <official_title>Involvement of Immune Cells Derived From the Intestine in Sjogren's Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Bordeaux</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>
      The study aims at defining the role of immune cells derived from the intestine in the&#xD;
      pathogenesis of Sjogren's disease. This research might open new therapeutic approaches for&#xD;
      the treatment of autoimmune diseases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autoimmune diseases are characterized by a loss of tolerance of the immune system for&#xD;
      self-antigens. One of the feature of autoimmune diseases is the infiltration of lymphoid&#xD;
      cells in the tissues damaged by the disease (i.e. kidney in systemic lupus erythematous or&#xD;
      brain in multiple sclerosis). However, the origins and properties of the immune cells&#xD;
      infiltrating these target tissues are largely unknown.&#xD;
&#xD;
      Studies in mouse models have shown that the composition of the gut microbiota can modify the&#xD;
      susceptibility to autoimmune diseases. These studies demonstrated that the microbiota&#xD;
      composition can alter the pathogenic properties of T cells in the gut but also in the target&#xD;
      tissues. For instance, in the experimental autoimmune encephalomyelitis model, the&#xD;
      composition of the gut microbiota has been shown to modulate the susceptibility to the&#xD;
      disease and the properties of the pathogenic CD4 T cells in the gut but also in the central&#xD;
      nervous system. In human an alteration in the composition of the gut microbiota is observed&#xD;
      in numerous autoimmune diseases, including Sjogren's syndrome, suggesting that perturbation&#xD;
      of the gut microbiota might be linked to the pathogenicity of immune cells in the target&#xD;
      organs. However, the mechanisms by which the microbiota impacts the pathogenicity of immune&#xD;
      cells in the target organs is unknown. It is proposed that gut immune cells directly exposed&#xD;
      to the microbiota compounds could migrate to the target organs and participate to the buildup&#xD;
      of tissue damages. This hypothesis is supported by studies in mouse models showing the&#xD;
      migration of gut CD4 T cells in the inflamed kidney (glomerulonephritis model) or in the&#xD;
      systemic lymphoid organs (rheumatoid arthritis model). The preliminary data support this&#xD;
      hypothesis as the investigators have shown that gut-derived CD4 T cells display pathogenic&#xD;
      properties in human autoimmune diseases. To determine whether and how the gut-derived immune&#xD;
      cells are involved in the pathogenesis of autoimmune disease, the investigators propose to&#xD;
      study the origin and properties of immune cells infiltrated in target tissues in autoimmune&#xD;
      diseases.&#xD;
&#xD;
      Sjogren's syndrome is a systemic autoimmune disease in which exocrine gland in particular&#xD;
      lacrimal and salivary glands are affected. One of the hallmark of the disease is the&#xD;
      infiltration of lymphoid cells in the exocrine glands of the patients. Indeed, the presence&#xD;
      of lymphoid infiltrate in the minor labial salivary gland of the patients is one of the most&#xD;
      important diagnostic tool for Sjogren's syndrome. The investigation of lymphoid infiltrates&#xD;
      requires to perform a biopsy of the labial salivary gland. The investigators propose here to&#xD;
      take advantage of this minimally invasive procedure to study the properties of the lymphoid&#xD;
      cells present in the minor salivary glands of Sjogren's patients.&#xD;
&#xD;
      The study will recruit 200 patients followed in Bordeaux University Hospital in which a&#xD;
      salivary gland biopsy is performed for a clinical suspicion of Sjogren's syndrome. Blood and&#xD;
      a biopsy of the minor salivary gland of the lip will be collected during a scheduled visit to&#xD;
      study the properties of infiltrated immune cells. Clinical and biological disease activity,&#xD;
      treatment and outcomes will be studied in correlation with the properties of infiltrated&#xD;
      immune cells. No extra visit will be needed and the biopsy of the minor salivary gland of the&#xD;
      lip and the blood samples will be collected at the same times as those collected for clinical&#xD;
      purposes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of the immune cells infiltrated in the minor salivary glands of Sjogren's patients.</measure>
    <time_frame>At baseline (Day 0)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quantification of disease activity scores for Sjogren's patients evalued by EULAR Sjögren Syndrome Disease Activity Index</measure>
    <time_frame>At baseline (Day 0)</time_frame>
    <description>EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) : between 0 and 123, in which higher values indicate higher severity</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Sjogren's Syndrome</condition>
  <arm_group>
    <arm_group_label>Sjogren's Syndrome</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>blood sample</intervention_name>
    <description>36 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation</description>
    <arm_group_label>Sjogren's Syndrome</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>biopsy of the labial salivary gland</intervention_name>
    <description>Part of the biopsy of the labial salivary gland</description>
    <arm_group_label>Sjogren's Syndrome</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Suspicion of Sjogren's syndrome based on 2016 American College of Rheumatology (ACR)&#xD;
             criteria;&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Being affiliated to health insurance&#xD;
&#xD;
          -  Willing to participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding women,&#xD;
&#xD;
          -  Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty&#xD;
             by a judicial or administrative decision, minors, persons of legal age who are the&#xD;
             object of a legal protection measure or unable to express their consent)&#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>Pierre DUFFAU, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Bordeaux</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pierre DUFFAU, Prof</last_name>
    <phone>(0)5 56 79 58 28</phone>
    <phone_ext>+33</phone_ext>
    <email>pierre.duffau@chu-bordeaux.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nathalie SCHMITT, PhD</last_name>
    <phone>(0)7 87 99 14 70</phone>
    <phone_ext>+33</phone_ext>
    <email>nathalie.schmitt@u-bordeaux.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU de Bordeaux - Service de médecine interne</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre DUFFAU, Prof</last_name>
      <phone>(0)5 56 79 58 28</phone>
      <phone_ext>+33</phone_ext>
      <email>pierre.duffau@chu-bordeaux.fr</email>
    </contact>
    <contact_backup>
      <last_name>Nathalie SCHMITT, PhD</last_name>
      <phone>(0)7 87 99 14 70</phone>
      <phone_ext>+33</phone_ext>
      <email>nathalie.schmitt@u-bordeaux.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Pierre DUFFAU, Prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Estibaliz LAZARO, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christophe RICHEZ, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>February 13, 2019</study_first_submitted>
  <study_first_submitted_qc>February 13, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>August 28, 2023</last_update_submitted>
  <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>lymphoid cells</keyword>
  <keyword>gut-derived lymphocytes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sjogren's Syndrome</mesh_term>
    <mesh_term>Syndrome</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/NCT03841318
org study id: CHUBX 2018/53
nct id: NCT03841318
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study aims at defining the role of immune cells derived from the intestine in the
      pathogenesis of Sjogren's disease. This research might open new therapeutic approaches for
      the treatment of autoimmune diseases.
Autoimmune diseases are characterized by a loss of tolerance of the immune system for
      self-antigens. One of the feature of autoimmune diseases is the infiltration of lymphoid
      cells in the tissues damaged by the disease (i.e. kidney in systemic lupus erythematous or
      brain in multiple sclerosis). However, the origins and properties of the immune cells
      infiltrating these target tissues are largely unknown.

      Studies in mouse models have shown that the composition of the gut microbiota can modify the
      susceptibility to autoimmune diseases. These studies demonstrated that the microbiota
      composition can alter the pathogenic properties of T cells in the gut but also in the target
      tissues. For instance, in the experimental autoimmune encephalomyelitis model, the
      composition of the gut microbiota has been shown to modulate the susceptibility to the
      disease and the properties of the pathogenic CD4 T cells in the gut but also in the central
      nervous system. In human an alteration in the composition of the gut microbiota is observed
      in numerous autoimmune diseases, including Sjogren's syndrome, suggesting that perturbation
      of the gut microbiota might be linked to the pathogenicity of immune cells in the target
      organs. However, the mechanisms by which the microbiota impacts the pathogenicity of immune
      cells in the target organs is unknown. It is proposed that gut immune cells directly exposed
      to the microbiota compounds could migrate to the target organs and participate to the buildup
      of tissue damages. This hypothesis is supported by studies in mouse models showing the
      migration of gut CD4 T cells in the inflamed kidney (glomerulonephritis model) or in the
      systemic lymphoid organs (rheumatoid arthritis model). The preliminary data support this
      hypothesis as the investigators have shown that gut-derived CD4 T cells display pathogenic
      properties in human autoimmune diseases. To determine whether and how the gut-derived immune
      cells are involved in the pathogenesis of autoimmune disease, the investigators propose to
      study the origin and properties of immune cells infiltrated in target tissues in autoimmune
      diseases.

      Sjogren's syndrome is a systemic autoimmune disease in which exocrine gland in particular
      lacrimal and salivary glands are affected. One of the hallmark of the disease is the
      infiltration of lymphoid cells in the exocrine glands of the patients. Indeed, the presence
      of lymphoid infiltrate in the minor labial salivary gland of the patients is one of the most
      important diagnostic tool for Sjogren's syndrome. The investigation of lymphoid infiltrates
      requires to perform a biopsy of the labial salivary gland. The investigators propose here to
      take advantage of this minimally invasive procedure to study the properties of the lymphoid
      cells present in the minor salivary glands of Sjogren's patients.

      The study will recruit 200 patients followed in Bordeaux University Hospital in which a
      salivary gland biopsy is performed for a clinical suspicion of Sjogren's syndrome. Blood and
      a biopsy of the minor salivary gland of the lip will be collected during a scheduled visit to
      study the properties of infiltrated immune cells. Clinical and biological disease activity,
      treatment and outcomes will be studied in correlation with the properties of infiltrated
      immune cells. No extra visit will be needed and the biopsy of the minor salivary gland of the
      lip and the blood samples will be collected at the same times as those collected for clinical
      purposes.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Quantification of the immune cells infiltrated in the minor salivary glands of Sjogren's patients.
time frame: At baseline (Day 0)
measure: Quantification of disease activity scores for Sjogren's patients evalued by EULAR Sjögren Syndrome Disease Activity Index
time frame: At baseline (Day 0)
description: EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) : between 0 and 123, in which higher values indicate higher severity
arm group label: Sjogren's Syndrome
arm group type: Experimental
intervention type: Biological
intervention name: blood sample
description: 36 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
arm group label: Sjogren's Syndrome
intervention type: Biological
intervention name: biopsy of the labial salivary gland
description: Part of the biopsy of the labial salivary gland
arm group label: Sjogren's Syndrome
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pierre DUFFAU, Prof
role: Principal Investigator
affiliation: CHU Bordeaux
last name: Pierre DUFFAU, Prof
phone: (0)5 56 79 58 28
phone ext: +33
email: pierre.duffau@chu-bordeaux.fr
last name: Nathalie SCHMITT, PhD
phone: (0)7 87 99 14 70
phone ext: +33
email: nathalie.schmitt@u-bordeaux.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Sjogren's Syndrome
mesh term: Syndrome
sharing ipd: No