<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/NCT03796611</url>
  </required_header>
  <id_info>
    <org_study_id>2016_04</org_study_id>
    <secondary_id>2017-A00835-48</secondary_id>
    <nct_id>NCT03796611</nct_id>
  </id_info>
  <brief_title>Phenotypic and Functional Study of 4BL B Cells in Multiple Sclerosis (MS)</brief_title>
  <acronym>4BLMS</acronym>
  <official_title>Phenotypic and Functional Study of 4BL B Cells in Multiple Sclerosis (MS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Lille</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>
      Recent works highlight the B cells involvement in multiple sclerosis (MS) pathology but their&#xD;
      role remains poorly understood. It was previously described that activated memory B cells&#xD;
      called 4BL due to the increased expression of 4-1BBL, an activation marker, induce&#xD;
      pro-inflammatory response by activating T CD8+ lymphocytes. Those 4BL cells are also&#xD;
      described in systemic inflammation in 80 years old people explaining the poor efficiency of&#xD;
      vaccination in that sub population. Those 4BL cells can also induce anti-tumoral T cell&#xD;
      response.&#xD;
&#xD;
      The hypothesize is that 4BL may induce a pathogenic inflammatory response in MS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      the aim to compare the proportion of peripheral (blood) 4 BL cells but also 4-BL cells in&#xD;
      cerebro spinal fluid (CSF) in MS compared to healthy controls and to other inflammatory&#xD;
      neurological disease but also non inflammatory neurological disease.&#xD;
&#xD;
      For all groups of patients and controls it will collect blood and CSF only once (at diagnosis&#xD;
      time for patients).&#xD;
&#xD;
      Blood collect from healthy controls will come from transfusion volunteers and we won't have&#xD;
      CSF from them.&#xD;
&#xD;
      For patients from the MS group, the blood collect will be sequential at diagnosis, 3, 6, 12&#xD;
      and 24 months after during the follow up.&#xD;
&#xD;
      In the blood and CSF we will evaluate:&#xD;
&#xD;
        -  percentage of 4 BL cells. 4 BL cells are found using cytometric parameters&#xD;
&#xD;
        -  capacity of 4 BL cells to induce inflammatory response in vitro: percentage of induced&#xD;
           activated TCD8 proliferation after cell culture using extracellular and intracellular&#xD;
           cytometric parameters&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 2020</start_date>
  <completion_date type="Anticipated">October 2022</completion_date>
  <primary_completion_date type="Anticipated">October 2022</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>the percentage of 4 BL cells in blood between MS patients and healthy controls</measure>
    <time_frame>Baseline: one session</time_frame>
    <description>4 BL are defined using cytometric parameters</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the percentage of 4 BL cells in blood between MS patients and patients with inflammatory and non inflammatory neurological disease</measure>
    <time_frame>Baseline: one session</time_frame>
    <description>4 BL are defined using cytometric parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the percentage of 4 BL cells in CSF between MS patients and patients with inflammatory and non inflammatory neurological disease</measure>
    <time_frame>Baseline: one session</time_frame>
    <description>4 BL are defined using cytometric parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>to analyse over time the evolution of 4BL percentages in blood in MS patients</measure>
    <time_frame>5 blood collection at baseline, 3, 6, 12, and 24 months after baseline</time_frame>
    <description>4 BL are defined using cytometric parameters</description>
  </secondary_outcome>
  <other_outcome>
    <measure>biological bank with mononuclear cells from all the groups fo that study</measure>
    <time_frame>through study completion, an average of 2 years</time_frame>
    <description>to constitute at Baseline a biological bank with mononuclear cells from all the groups fo that study</description>
  </other_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">172</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>multiple sclerosis patient</arm_group_label>
    <description>MS is defined according to McDonald criteria 2017. MS patients included have a disease duration of less than 1 year</description>
  </arm_group>
  <arm_group>
    <arm_group_label>other neurological inflammatory disease</arm_group_label>
    <description>autoimmune encephalitis, myasthenia gravis, chronic inflammatory demyelinating polyradiculitis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>neurological non inflammatory disease</arm_group_label>
    <description>benign intracranial hypertension, degenerative disorder</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy controls</arm_group_label>
    <description>transfusion volunteers from transfusion center</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood sampling and Cerebrospinal fluid at baseline and five sequential blood sampling for MS&#xD;
      groups&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        MS patients and controls: healthy controls and patients having non-MS neurological&#xD;
        inflammatory disease and patients having other non inflammatory neurological disease.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria for MS group:&#xD;
&#xD;
          -  MS defined by McDonald 2017 criteria with a disease duration of less than 1 year&#xD;
&#xD;
          -  between 18 and 60 years old patients&#xD;
&#xD;
          -  naïve of any immune therapy or steroid intake&#xD;
&#xD;
          -  patients who signed consent to the study&#xD;
&#xD;
        Inclusion Criteria for controls with inflammatory of non inflammatory neurological disease:&#xD;
&#xD;
          -  patients who signed consent to the study&#xD;
&#xD;
          -  between 18 and 60 years old patients&#xD;
&#xD;
          -  naïve of any steroid intake or immune therapy&#xD;
&#xD;
        Inclusion criteria for healthy controls:&#xD;
&#xD;
          -  control who signed consent at transfusion center for their blood collect to be used&#xD;
             for study&#xD;
&#xD;
          -  between 18 and 60 years old patients&#xD;
&#xD;
          -  naïve of any steroid intake or immune therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy or breast-feeding&#xD;
&#xD;
          -  patients or controls unable to sign the consent or to consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hélène ZEPHIR, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hélène ZEPHIR, MD, PhD</last_name>
    <phone>3 20 44 68 46</phone>
    <phone_ext>+33</phone_ext>
    <email>helene.zephir@chru-lille.fr</email>
  </overall_contact>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>September 14, 2020</last_update_submitted>
  <last_update_submitted_qc>September 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>immunology</keyword>
  <keyword>B cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT03796611
org study id: 2016_04
secondary id: 2017-A00835-48
nct id: NCT03796611
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Recent works highlight the B cells involvement in multiple sclerosis (MS) pathology but their
      role remains poorly understood. It was previously described that activated memory B cells
      called 4BL due to the increased expression of 4-1BBL, an activation marker, induce
      pro-inflammatory response by activating T CD8+ lymphocytes. Those 4BL cells are also
      described in systemic inflammation in 80 years old people explaining the poor efficiency of
      vaccination in that sub population. Those 4BL cells can also induce anti-tumoral T cell
      response.

      The hypothesize is that 4BL may induce a pathogenic inflammatory response in MS.
the aim to compare the proportion of peripheral (blood) 4 BL cells but also 4-BL cells in
      cerebro spinal fluid (CSF) in MS compared to healthy controls and to other inflammatory
      neurological disease but also non inflammatory neurological disease.

      For all groups of patients and controls it will collect blood and CSF only once (at diagnosis
      time for patients).

      Blood collect from healthy controls will come from transfusion volunteers and we won't have
      CSF from them.

      For patients from the MS group, the blood collect will be sequential at diagnosis, 3, 6, 12
      and 24 months after during the follow up.

      In the blood and CSF we will evaluate:

        -  percentage of 4 BL cells. 4 BL cells are found using cytometric parameters

        -  capacity of 4 BL cells to induce inflammatory response in vitro: percentage of induced
           activated TCD8 proliferation after cell culture using extracellular and intracellular
           cytometric parameters
observational model: Case-Control
time perspective: Prospective
measure: the percentage of 4 BL cells in blood between MS patients and healthy controls
time frame: Baseline: one session
description: 4 BL are defined using cytometric parameters
measure: the percentage of 4 BL cells in blood between MS patients and patients with inflammatory and non inflammatory neurological disease
time frame: Baseline: one session
description: 4 BL are defined using cytometric parameters
measure: the percentage of 4 BL cells in CSF between MS patients and patients with inflammatory and non inflammatory neurological disease
time frame: Baseline: one session
description: 4 BL are defined using cytometric parameters
measure: to analyse over time the evolution of 4BL percentages in blood in MS patients
time frame: 5 blood collection at baseline, 3, 6, 12, and 24 months after baseline
description: 4 BL are defined using cytometric parameters
measure: biological bank with mononuclear cells from all the groups fo that study
time frame: through study completion, an average of 2 years
description: to constitute at Baseline a biological bank with mononuclear cells from all the groups fo that study
arm group label: multiple sclerosis patient
description: MS is defined according to McDonald criteria 2017. MS patients included have a disease duration of less than 1 year
arm group label: other neurological inflammatory disease
description: autoimmune encephalitis, myasthenia gravis, chronic inflammatory demyelinating polyradiculitis
arm group label: neurological non inflammatory disease
description: benign intracranial hypertension, degenerative disorder
arm group label: healthy controls
description: transfusion volunteers from transfusion center
blood sampling and Cerebrospinal fluid at baseline and five sequential blood sampling for MS
      groups
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Hélène ZEPHIR, MD, PhD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Hélène ZEPHIR, MD, PhD
phone: 3 20 44 68 46
phone ext: +33
email: helene.zephir@chru-lille.fr
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis