<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/NCT04440566</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2020/06</org_study_id>
    <nct_id>NCT04440566</nct_id>
  </id_info>
  <brief_title>O-GlcNAcylation Role in the Pathophysiology of Systemic Lupus Erythematosus</brief_title>
  <acronym>METABOLUPS</acronym>
  <official_title>O-GlcNAcylation Role in the Pathophysiology of Systemic Lupus Erythematosus</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>
      This study aims at defining the role of O-GlcNAcylation is in the physiopathology of systemic&#xD;
      lupus erythematosus (SLE). O-GlcNAcylation is a metabolic pathway potentially implicated in&#xD;
      SLE with potential for the discovery of new therapeutic strategies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Systemic lupus erythematosus (SLE) is a rare and potentially life-threatening auto-immune&#xD;
      systemic disease. There is an urgent need for better comprehension of the physiopathology of&#xD;
      the disease and to discover new therapeutic pathways.&#xD;
&#xD;
      The hexosamine biosynthesis pathway, or HBP, is an important regulator of immunity and&#xD;
      results in a post-transductional modification of proteins called O-GlcNAcylation and involved&#xD;
      in inflammation and immunity.&#xD;
&#xD;
      There is a very unbalanced sex ratio in favor of women in SLE suggesting a role of the X&#xD;
      chromosome in the physiopathology of the disease. The human OGT gene (a key O-GlcNAcylation&#xD;
      enzyme) is localized on the X chromosome, near the XIST gene responsible for the inactivation&#xD;
      of one X chromosome by methylation.&#xD;
&#xD;
      Moreover, genes encoding CD40L, CXCR3 and OGT have been shown to be demethylated and&#xD;
      overexpressed in T cells of women with systemic systemic lupus erythematosus compared to men&#xD;
      with the same pathology.&#xD;
&#xD;
      The investigators hypothesize that O-GlcNAcylation is increased in the effector lymphocytes&#xD;
      of SLE patients and involved in the pathophysiology of the disease. Therefore, inhibiting&#xD;
      O-GlcNAcylation may be a promising therapeutic option in SLE.&#xD;
&#xD;
      This study will recruit 100 patients with SLE followed in Bordeaux University Hospital. Among&#xD;
      classical disease activity information, blood samples will be collected at study visit to&#xD;
      study O-GlcNAcylation levels in immune cells. Fundamental research will be realized on&#xD;
      patients' sample.&#xD;
&#xD;
      Clinical and biological disease activity, treatment and outcomes will be studied in&#xD;
      correlation with O-GlcNAcylation levels. Patients will be included within their usual&#xD;
      follow-up. No extra visit will be needed and blood samples will be drawn at the same times as&#xD;
      those drawn for clinical purposes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 13, 2020</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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 O-GlcNAcylation level in the blood samples of SLE</measure>
    <time_frame>At baseline (Day 0)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)</measure>
    <time_frame>At baseline (Day 0)</time_frame>
    <description>score (Min value: 0 - Max value: 105), with higher values mean higher disease activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease activity according to British Lupus Assessment Group Index 2004 (BILAG-2004)</measure>
    <time_frame>At baseline (Day 0)</time_frame>
    <description>(Min value : 0 - Max value : 4), with higher values mean more severe symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of OGT biallelic expression in the blood samples of SLE</measure>
    <time_frame>At baseline (Day 0)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Systemic Lupus Erythematosus</condition>
  <arm_group>
    <arm_group_label>Systemic lupus erythematosus (SLE)</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>30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation</description>
    <arm_group_label>Systemic lupus erythematosus (SLE)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patient aged over 18 years old&#xD;
&#xD;
          -  Diagnosis of systemic lupus erythematosus&#xD;
&#xD;
          -  Affiliated person or beneficiary of a social security scheme.&#xD;
&#xD;
          -  Having signed an informed consent (at the latest on the day of inclusion and before&#xD;
             any examination required by research).&#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>Patrick BLANCO, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Bordeaux</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Patrick BLANCO, Prof</last_name>
    <phone>(0)5 56 79 56 45</phone>
    <phone_ext>+33</phone_ext>
    <email>patrick.blanco@chu-bordeaux.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thomas BARNETCHE, PhD</last_name>
    <phone>(0)5 57 82 04 93</phone>
    <phone_ext>+33</phone_ext>
    <email>thomas.barnetche@chu-bordeaux.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU de Bordeaux - Service d'Immunologie et Immunogénétique</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick BLANCO, Prof</last_name>
      <phone>(0)5 56 79 56 45</phone>
      <phone_ext>+33</phone_ext>
      <email>patrick.blanco@chu-bordeaux.fr</email>
    </contact>
    <contact_backup>
      <last_name>Thomas BARNETCHE, PhD</last_name>
      <phone>(0)5.57.82.04.93</phone>
      <phone_ext>+33</phone_ext>
      <email>thomas.barnetche@chu-bordeaux.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Patrick BLANCO, Prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christophe RICHEZ, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lionel COUZI, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pierre DUFFAU, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Julien SENESCHAL, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Estibaliz LAZARO, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>November 14, 2022</last_update_submitted>
  <last_update_submitted_qc>November 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Systemic lupus erythematosus</keyword>
  <keyword>autoimmunity</keyword>
  <keyword>O-GlcNAcylation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</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/NCT04440566
org study id: CHUBX 2020/06
nct id: NCT04440566
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims at defining the role of O-GlcNAcylation is in the physiopathology of systemic
      lupus erythematosus (SLE). O-GlcNAcylation is a metabolic pathway potentially implicated in
      SLE with potential for the discovery of new therapeutic strategies.
Systemic lupus erythematosus (SLE) is a rare and potentially life-threatening auto-immune
      systemic disease. There is an urgent need for better comprehension of the physiopathology of
      the disease and to discover new therapeutic pathways.

      The hexosamine biosynthesis pathway, or HBP, is an important regulator of immunity and
      results in a post-transductional modification of proteins called O-GlcNAcylation and involved
      in inflammation and immunity.

      There is a very unbalanced sex ratio in favor of women in SLE suggesting a role of the X
      chromosome in the physiopathology of the disease. The human OGT gene (a key O-GlcNAcylation
      enzyme) is localized on the X chromosome, near the XIST gene responsible for the inactivation
      of one X chromosome by methylation.

      Moreover, genes encoding CD40L, CXCR3 and OGT have been shown to be demethylated and
      overexpressed in T cells of women with systemic systemic lupus erythematosus compared to men
      with the same pathology.

      The investigators hypothesize that O-GlcNAcylation is increased in the effector lymphocytes
      of SLE patients and involved in the pathophysiology of the disease. Therefore, inhibiting
      O-GlcNAcylation may be a promising therapeutic option in SLE.

      This study will recruit 100 patients with SLE followed in Bordeaux University Hospital. Among
      classical disease activity information, blood samples will be collected at study visit to
      study O-GlcNAcylation levels in immune cells. Fundamental research will be realized on
      patients' sample.

      Clinical and biological disease activity, treatment and outcomes will be studied in
      correlation with O-GlcNAcylation levels. Patients will be included within their usual
      follow-up. No extra visit will be needed and blood samples will be drawn at the same times as
      those drawn for clinical purposes.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Quantification of O-GlcNAcylation level in the blood samples of SLE
time frame: At baseline (Day 0)
measure: Disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
time frame: At baseline (Day 0)
description: score (Min value: 0 - Max value: 105), with higher values mean higher disease activity.
measure: Disease activity according to British Lupus Assessment Group Index 2004 (BILAG-2004)
time frame: At baseline (Day 0)
description: (Min value : 0 - Max value : 4), with higher values mean more severe symptoms
measure: Quantification of OGT biallelic expression in the blood samples of SLE
time frame: At baseline (Day 0)
arm group label: Systemic lupus erythematosus (SLE)
arm group type: Experimental
intervention type: Biological
intervention name: blood sample
description: 30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
arm group label: Systemic lupus erythematosus (SLE)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick BLANCO, Prof
role: Principal Investigator
affiliation: CHU Bordeaux
last name: Patrick BLANCO, Prof
phone: (0)5 56 79 56 45
phone ext: +33
email: patrick.blanco@chu-bordeaux.fr
last name: Thomas BARNETCHE, PhD
phone: (0)5 57 82 04 93
phone ext: +33
email: thomas.barnetche@chu-bordeaux.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
sharing ipd: No