<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/NCT04463550</url>
  </required_header>
  <id_info>
    <org_study_id>GFAP</org_study_id>
    <nct_id>NCT04463550</nct_id>
  </id_info>
  <brief_title>GFAP Auto-immunity : a French Cohort Study</brief_title>
  <acronym>GFAP</acronym>
  <official_title>GFAP Auto-immunity : a French Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Glial fibrillary acidic protein (GFAP)-Immunoglobulin G (IgG) have recently been described as&#xD;
      a biomarker of a novel inflammatory central nervous system (CNS) disorder, termed autoimmune&#xD;
      GFAP astrocytopathy. Thus far, four major clinical series have been published (two from Mayo&#xD;
      Clinic USA, one from Italy and one from China). GFAP-IgG detected in serum or in&#xD;
      cerebrospinal fluid, by tissue-based assay and confirmed by cell-based assay, are associated&#xD;
      with encephalitis or meningoencephalitis of acute or subacute onset, less frequently with&#xD;
      myelitis or optic disk edema. The characteristic MRI feature is brain linear perivascular&#xD;
      radial gadolinium enhancement in the white matter perpendicular to the ventricle, consistent&#xD;
      with the immunohistochemical staining pattern of GFAP in rodent brain sections. Approximately&#xD;
      20% of reported cases are associated with a neoplasm (ovarian teratoma mostly). Coexisting&#xD;
      neural autoantibodies are described in some patients, N-methyl-D-aspartate (NMDA)-receptor&#xD;
      (R)-IgG mostly, followed by aquaporin 4 (AQP4)-IgG. The disease is usually corticosteroid&#xD;
      responsive although relapse can occur. In contrast, Chinese patients display poorer outcomes.&#xD;
      Pathophysiology is not well understood but the intracellular antigen location makes GFAP-IgG&#xD;
      unlikely pathogenic whereas animal models and neuropathologic data suggest a T-cell&#xD;
      immune-mediated disorder.&#xD;
&#xD;
      The aim of the investigators is to report the first French cohort of patients GFAP-IgG&#xD;
      positive. Investigators retrospectively assessed clinical, immunological and radiological&#xD;
      features, treatment response and outcomes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Anticipated">November 1, 2020</completion_date>
  <primary_completion_date type="Actual">January 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Report retrospectively clinical data of patients GFAP-IgG positive.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe prodromes (yes or no), neurologic signs and clinical course (acute/subacute - yes or&#xD;
no - or progressive onset - yes or no), if admitted in intensive care units (yes or no), retrospectively provided by&#xD;
the treating physicians using a structured questionnaire.or progressive onset), if admitted in intensive care units, neoplastic and dysimmune associated diseases and T cell dysregulation condition .</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Describe GFAP-antibody test results.</measure>
    <time_frame>13 months</time_frame>
    <description>positivity of GFAP α -IgG in cerebrospinal fluid, in serum and isoform type at diagnostic and follow up.&#xD;
positivity of GFAP α -IgG in cerebrospinal fluid, in serum and isoform type at diagnostic and follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>demographic data of patients GFAP-IgG positive : age at onset</measure>
    <time_frame>13 months</time_frame>
    <description>age at onset (years) retrospectively provided by the treating&#xD;
physicians using a structured questionnaire</description>
  </secondary_outcome>
  <other_outcome>
    <measure>demographic data of patients GFAP-IgG positive : phenotype</measure>
    <time_frame>13 months</time_frame>
    <description>Report if caucasian (yes or no) retrospectively provided by the treating&#xD;
physicians using a structured questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>demographic data of patients GFAP-IgG positive : sex</measure>
    <time_frame>13 months</time_frame>
    <description>Report if female sex (yes or no) retrospectively provided by the treating&#xD;
physicians using a structured questionnaire&#xD;
physicians using a structured questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>associated conditions of patients GFAP-IgG positive</measure>
    <time_frame>13 months</time_frame>
    <description>Report if neoplastic and dysimmune associated diseases and T cell dysregulation condition (yes or no)&#xD;
physicians using a structured questionnaire&#xD;
physicians using a structured questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Report cerebrospinal fluid white cell count</measure>
    <time_frame>13 months</time_frame>
    <description>white cell count (/mm3)</description>
  </other_outcome>
  <other_outcome>
    <measure>Report cerebrospinal fluid protein level</measure>
    <time_frame>13 months</time_frame>
    <description>protein level (g/L)</description>
  </other_outcome>
  <other_outcome>
    <measure>Report cerebrospinal fluid glucose level</measure>
    <time_frame>13 months</time_frame>
    <description>glucose level (mmol/L)</description>
  </other_outcome>
  <other_outcome>
    <measure>Report number of oligoclonal bands in cerebrospinal fluid</measure>
    <time_frame>13 months</time_frame>
    <description>number of oligoclonal bands</description>
  </other_outcome>
  <other_outcome>
    <measure>Describe MRI features.</measure>
    <time_frame>13 months</time_frame>
    <description>Head and medullar MRI at diagnostic and follow up were reviewed by a neuroradiologist. scale) at each relapse and last follow up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Report other paraclinic findings : electroencephalographic results.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe electroencephalographic results at diagnostic and follow up when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report other paraclinic findings : electromyographic results.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe electromyographic results at diagnostic and follow up when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report ophthalmic exam : visual acuity</measure>
    <time_frame>13 months</time_frame>
    <description>Describe visual acuity (/10) at diagnostic and follow up when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report ophthalmic exam : ocular fundus.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe ocular fundus at diagnostic and follow up results when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report ophthalmic exam : visual field.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe visual field at diagnostic and follow up when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report ophthalmic exam : optical coherence tomography.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe optical coherence tomography (RNFL thickness) at diagnostic and follow up when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report histologic findings.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe histologic results at diagnostic and follow up when done .</description>
  </other_outcome>
  <other_outcome>
    <measure>Report treatments and response.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe acute and long-term treatments administered and response.</description>
  </other_outcome>
  <other_outcome>
    <measure>Report outcome.</measure>
    <time_frame>13 months</time_frame>
    <description>Describe outcome (modified Rankin scale) at each relapse and last follow up.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">38</enrollment>
  <condition>Autoimmune GFAP Astrocytopathy</condition>
  <arm_group>
    <arm_group_label>Patients GFAP-IgG positive in serum and/or CSF</arm_group_label>
    <description>Patients developing clinical autoimmune encephalitis or meningoencephalomyelitis with anti-GFAP antibodies, managed by the National Reference Center for Paraneoplastic Syndromes and Autoimmune Encephalitis or the National Reference Center for Centre de référence for Neuro-inflammatory diseases of the brain and the spinal cord at the Neurological Hospital of Bron.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Description and analysis</intervention_name>
    <description>Retrospective, non-interventional study, using clinical, biological, radiological and therapeutic data collected during the initial diagnosis and follow-up.</description>
    <arm_group_label>Patients GFAP-IgG positive in serum and/or CSF</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients GFAP-IgG positive in serum and/or CSF&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Positive GFAP-Ab in serum and/or CSF tested by immunohistochemistry on mouse brain&#xD;
             slices and confirmed by cell-based assay (CBA) of HEK293 cells expressing GFAP.&#xD;
&#xD;
          -  Diagnosis and follow-up in France&#xD;
&#xD;
          -  No age limit : from 0 to unlimited age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients GFAP-IgG negative in serum and CSF&#xD;
&#xD;
          -  Absence of complete clinicopathological data&#xD;
&#xD;
          -  Foreign follow-up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Romain MARIGNIER</last_name>
    <role>Study Director</role>
    <affiliation>Centre de référence des maladies inflammatoires rares du cerveau et de la moelle, Lyon, France</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Romain MARIGNIER, Dr</last_name>
    <phone>04-72-35-75-22</phone>
    <email>romain.marignier@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Géraldine PICARD</last_name>
    <phone>04 72 35 58 42</phone>
    <email>geraldine.picard@chu-lyon.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Bron</city>
        <zip>69250</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Romain MARIGNIER</last_name>
      <phone>04-72-35-75-22</phone>
      <email>romain.marignier@chu-lyon.fr</email>
    </contact>
    <contact_backup>
      <last_name>Géraldine PICARD</last_name>
      <phone>04 72 35 58 42</phone>
      <email>geraldine.picard@chu-lyon.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>April 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>July 3, 2020</last_update_submitted>
  <last_update_submitted_qc>July 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acidic Protein IgG</keyword>
  <keyword>astrocytopathy</keyword>
  <keyword>meningoencephalomyelitis</keyword>
  <keyword>perivascular-radial parenchymal enhancement</keyword>
  <keyword>autoimmune</keyword>
  <keyword>paraneoplasic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autoimmune Diseases</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/NCT04463550
org study id: GFAP
nct id: NCT04463550
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Glial fibrillary acidic protein (GFAP)-Immunoglobulin G (IgG) have recently been described as
      a biomarker of a novel inflammatory central nervous system (CNS) disorder, termed autoimmune
      GFAP astrocytopathy. Thus far, four major clinical series have been published (two from Mayo
      Clinic USA, one from Italy and one from China). GFAP-IgG detected in serum or in
      cerebrospinal fluid, by tissue-based assay and confirmed by cell-based assay, are associated
      with encephalitis or meningoencephalitis of acute or subacute onset, less frequently with
      myelitis or optic disk edema. The characteristic MRI feature is brain linear perivascular
      radial gadolinium enhancement in the white matter perpendicular to the ventricle, consistent
      with the immunohistochemical staining pattern of GFAP in rodent brain sections. Approximately
      20% of reported cases are associated with a neoplasm (ovarian teratoma mostly). Coexisting
      neural autoantibodies are described in some patients, N-methyl-D-aspartate (NMDA)-receptor
      (R)-IgG mostly, followed by aquaporin 4 (AQP4)-IgG. The disease is usually corticosteroid
      responsive although relapse can occur. In contrast, Chinese patients display poorer outcomes.
      Pathophysiology is not well understood but the intracellular antigen location makes GFAP-IgG
      unlikely pathogenic whereas animal models and neuropathologic data suggest a T-cell
      immune-mediated disorder.

      The aim of the investigators is to report the first French cohort of patients GFAP-IgG
      positive. Investigators retrospectively assessed clinical, immunological and radiological
      features, treatment response and outcomes.
observational model: Cohort
time perspective: Retrospective
measure: Report retrospectively clinical data of patients GFAP-IgG positive.
time frame: 13 months
description: Describe prodromes (yes or no), neurologic signs and clinical course (acute/subacute - yes or
no - or progressive onset - yes or no), if admitted in intensive care units (yes or no), retrospectively provided by
the treating physicians using a structured questionnaire.or progressive onset), if admitted in intensive care units, neoplastic and dysimmune associated diseases and T cell dysregulation condition .
measure: Describe GFAP-antibody test results.
time frame: 13 months
description: positivity of GFAP α -IgG in cerebrospinal fluid, in serum and isoform type at diagnostic and follow up.
positivity of GFAP α -IgG in cerebrospinal fluid, in serum and isoform type at diagnostic and follow up.
measure: demographic data of patients GFAP-IgG positive : age at onset
time frame: 13 months
description: age at onset (years) retrospectively provided by the treating
physicians using a structured questionnaire
measure: demographic data of patients GFAP-IgG positive : phenotype
time frame: 13 months
description: Report if caucasian (yes or no) retrospectively provided by the treating
physicians using a structured questionnaire
measure: demographic data of patients GFAP-IgG positive : sex
time frame: 13 months
description: Report if female sex (yes or no) retrospectively provided by the treating
physicians using a structured questionnaire
physicians using a structured questionnaire
measure: associated conditions of patients GFAP-IgG positive
time frame: 13 months
description: Report if neoplastic and dysimmune associated diseases and T cell dysregulation condition (yes or no)
physicians using a structured questionnaire
physicians using a structured questionnaire
measure: Report cerebrospinal fluid white cell count
time frame: 13 months
description: white cell count (/mm3)
measure: Report cerebrospinal fluid protein level
time frame: 13 months
description: protein level (g/L)
measure: Report cerebrospinal fluid glucose level
time frame: 13 months
description: glucose level (mmol/L)
measure: Report number of oligoclonal bands in cerebrospinal fluid
time frame: 13 months
description: number of oligoclonal bands
measure: Describe MRI features.
time frame: 13 months
description: Head and medullar MRI at diagnostic and follow up were reviewed by a neuroradiologist. scale) at each relapse and last follow up.
measure: Report other paraclinic findings : electroencephalographic results.
time frame: 13 months
description: Describe electroencephalographic results at diagnostic and follow up when done .
measure: Report other paraclinic findings : electromyographic results.
time frame: 13 months
description: Describe electromyographic results at diagnostic and follow up when done .
measure: Report ophthalmic exam : visual acuity
time frame: 13 months
description: Describe visual acuity (/10) at diagnostic and follow up when done .
measure: Report ophthalmic exam : ocular fundus.
time frame: 13 months
description: Describe ocular fundus at diagnostic and follow up results when done .
measure: Report ophthalmic exam : visual field.
time frame: 13 months
description: Describe visual field at diagnostic and follow up when done .
measure: Report ophthalmic exam : optical coherence tomography.
time frame: 13 months
description: Describe optical coherence tomography (RNFL thickness) at diagnostic and follow up when done .
measure: Report histologic findings.
time frame: 13 months
description: Describe histologic results at diagnostic and follow up when done .
measure: Report treatments and response.
time frame: 13 months
description: Describe acute and long-term treatments administered and response.
measure: Report outcome.
time frame: 13 months
description: Describe outcome (modified Rankin scale) at each relapse and last follow up.
arm group label: Patients GFAP-IgG positive in serum and/or CSF
description: Patients developing clinical autoimmune encephalitis or meningoencephalomyelitis with anti-GFAP antibodies, managed by the National Reference Center for Paraneoplastic Syndromes and Autoimmune Encephalitis or the National Reference Center for Centre de référence for Neuro-inflammatory diseases of the brain and the spinal cord at the Neurological Hospital of Bron.
intervention type: Other
intervention name: Description and analysis
description: Retrospective, non-interventional study, using clinical, biological, radiological and therapeutic data collected during the initial diagnosis and follow-up.
arm group label: Patients GFAP-IgG positive in serum and/or CSF
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Romain MARIGNIER
role: Study Director
affiliation: Centre de référence des maladies inflammatoires rares du cerveau et de la moelle, Lyon, France
last name: Romain MARIGNIER, Dr
phone: 04-72-35-75-22
email: romain.marignier@chu-lyon.fr
last name: Géraldine PICARD
phone: 04 72 35 58 42
email: geraldine.picard@chu-lyon.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Autoimmune Diseases
sharing ipd: No