<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/NCT04421846</url>
  </required_header>
  <id_info>
    <org_study_id>APHP200306</org_study_id>
    <secondary_id>2020-A00053-36</secondary_id>
    <nct_id>NCT04421846</nct_id>
  </id_info>
  <brief_title>Study of Pathophysiology of Status Epilepticus and Dysimmune Encephalitis</brief_title>
  <acronym>COLETTE</acronym>
  <official_title>COLETTE : Study of the Pathophysiology of Status Epilepticus and Dysimmune Encephalitis and Identification of Valuable Biomarkers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      COLETTE is an interventional study for which blood, cerebrospinal fluid and post-mortem&#xD;
      tissues are collected in patients with status epilepticus or epilepsy associated to dysimmune&#xD;
      encephalitis as well as in control patients, to better understand the pathophysiology of&#xD;
      these severe epileptic disorders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Epilepsy is one of the most common neurological condition which concerns around 50 million&#xD;
      people worldwide. Epilepsy is characterized by a lasting predisposition to generate seizures.&#xD;
      Epilepsy can present as heterogenous set of clinical symptoms and is related to extremely&#xD;
      varied etiologies. Some epilepsies are triggered by antineuronal autoantibodies and/or&#xD;
      complicated by a status epilepticus. These conditions may induce brain atrophy, and severe&#xD;
      neurological sequels.&#xD;
&#xD;
      The severity of these epilepsies requires significant efforts to (i) identify new therapeutic&#xD;
      strategies able to control the evolution of dysimmune encephalitis and refractory status&#xD;
      epilepticus, (ii) to identify their etiologies and (iii) to propose neuroprotective&#xD;
      strategies.&#xD;
&#xD;
      Therefore, the investigators will organize a collection of biological samples (blood,&#xD;
      cerebrospinal fluid, post-mortem brain tissues) and paraclinical data (electroencephalogram,&#xD;
      evoked potential, CT, MRI) in patients with severe epilepsies, whether or not associated with&#xD;
      autoantibodies, and/or evolving into status epilepticus.&#xD;
&#xD;
      This study should bring new insights allowing to better understand mechanisms that trigger&#xD;
      the emergence of an epileptic brain (epileptogenesis) through :&#xD;
&#xD;
      (i) the identification and characterization of new pathophysiological pathways involving&#xD;
      autoimmunity directed against the cerebral cortex and associated with severe epilepsy (ii)&#xD;
      the identification and characterization of pathophysiological pathways participating in the&#xD;
      excitotoxicity observed in status epilepticus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 25, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2027</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>Identification of (i) antibodies in the plasma and in the cerebrospinal fluid of patients with dysimmune encephalitis and (ii) biomarkers for neuronal death in the plasma and in the cerebrospinal fluid of patients with status epilepticus</measure>
    <time_frame>9 months</time_frame>
    <description>Looking for antibodies with cell-based binding assay or monospecific recombinant assay. Identification of biomarkers for neuronal death with electrochemiluminometric sandwich immunoassays (Kryptor and ModularE170, Roche Diagnostic)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identification of new dysimmune abnormalities</measure>
    <time_frame>9 months</time_frame>
    <description>Lymphocyte phenotyping, cytokines quantification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of specific EEG patterns associated to dysimmune encephalitis and/or status epilepticus</measure>
    <time_frame>9 months</time_frame>
    <description>EEG signals will be reviewed and classifiyed according to a EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of new genetic pathways associated to dysimmune encephalitis and status</measure>
    <time_frame>9 months</time_frame>
    <description>Genetic biomarkers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of new metabolic pathway that may participate in the excitotoxicity observed in status epilepticus or dysimmune encephalitis</measure>
    <time_frame>9 months</time_frame>
    <description>Looking for diagnostic and prognosis biomarkers. Characterization of the brain cholesterol homeostasis with UPLC-MS/MS method and enzymatic assays. Evaluation of new biomarkers (proteins, lipids, genes).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Status Epilepticus</condition>
  <condition>Dysimmune Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Group 1 : Status epilepticus</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 : Dysimmune encephalitis</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3 : Control patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)</intervention_name>
    <description>Collection of biological samples and clinical/paraclinical data</description>
    <arm_group_label>Group 1 : Status epilepticus</arm_group_label>
    <arm_group_label>Group 2 : Dysimmune encephalitis</arm_group_label>
    <arm_group_label>Group 3 : Control patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Group 1:&#xD;
&#xD;
          -  Patients aged 2 years or above, with status epilepticus.&#xD;
&#xD;
          -  Affiliation to a French social security system excluding &quot;Aide Médicale&quot; Etat (AME).&#xD;
&#xD;
          -  Patients or relatives have been informed and given free informed and written consent&#xD;
             to participate&#xD;
&#xD;
          -  Patients under legal protection (guardianship, curatorship) or not&#xD;
&#xD;
        Group 2:&#xD;
&#xD;
          -  Patients aged 2 years or above, with clinical signs of epilepsy associated to&#xD;
             dysimmune encephalitis.&#xD;
&#xD;
          -  Affiliation to a French social security system excluding &quot;Aide Médicale&quot; Etat (AME).&#xD;
&#xD;
          -  Patients or relatives have been informed and given free informed and written consent&#xD;
             to participate&#xD;
&#xD;
          -  Patients under legal protection (guardianship, curatorship) or not&#xD;
&#xD;
        Group 3:&#xD;
&#xD;
          -  Patients aged 18 years or above, without status epilepticus and/or dysimmune&#xD;
             encephalitis.&#xD;
&#xD;
          -  Affiliation to a French social security system excluding &quot;Aide Médicale&quot; Etat (AME).&#xD;
&#xD;
          -  Patients or relatives have been informed and given free informed and written consent&#xD;
             to participate&#xD;
&#xD;
          -  Patients under legal protection (guardianship, curatorship) or not&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Group 1:&#xD;
&#xD;
          -  Women with known or clinically detected pregnancy.&#xD;
&#xD;
          -  Patient deprived of liberty&#xD;
&#xD;
          -  Patients with known neurodegenerative disease.&#xD;
&#xD;
        Group 2:&#xD;
&#xD;
          -  Women with known or clinically detected pregnancy.&#xD;
&#xD;
          -  Patient deprived of liberty&#xD;
&#xD;
          -  Patients have been already treated by corticoids or IgIV.&#xD;
&#xD;
        Group 3:&#xD;
&#xD;
          -  Women with known or clinically detected pregnancy.&#xD;
&#xD;
          -  Patient deprived of liberty.&#xD;
&#xD;
          -  Patients with status epilepticus.&#xD;
&#xD;
          -  Patients with known neurodegenerative disease, brain tumor, severe head trauma,&#xD;
             meningitis, subarachnoid hemorrhages, stroke.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vincent NAVARRO, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Pitié Salpêtrière - Assitance Publique Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vincent NAVARRO, Pr</last_name>
    <phone>01 42 16 19 40</phone>
    <email>vincent.navarro@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital de la Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vincent NAVARRO, Pr</last_name>
      <phone>01 42 16 19 40</phone>
      <email>vincent.navarro@aphp.fr</email>
    </contact>
    <contact_backup>
      <last_name>Virginie LAMBRECQ, Dr</last_name>
      <phone>01 57 27 46 63</phone>
      <email>virginie.lambrecq@aphp.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Epilepsy</keyword>
  <keyword>Status Epilepticus</keyword>
  <keyword>Autoimmunity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Encephalitis</mesh_term>
    <mesh_term>Status Epilepticus</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/NCT04421846
org study id: APHP200306
secondary id: 2020-A00053-36
nct id: NCT04421846
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
COLETTE is an interventional study for which blood, cerebrospinal fluid and post-mortem
      tissues are collected in patients with status epilepticus or epilepsy associated to dysimmune
      encephalitis as well as in control patients, to better understand the pathophysiology of
      these severe epileptic disorders.
Epilepsy is one of the most common neurological condition which concerns around 50 million
      people worldwide. Epilepsy is characterized by a lasting predisposition to generate seizures.
      Epilepsy can present as heterogenous set of clinical symptoms and is related to extremely
      varied etiologies. Some epilepsies are triggered by antineuronal autoantibodies and/or
      complicated by a status epilepticus. These conditions may induce brain atrophy, and severe
      neurological sequels.

      The severity of these epilepsies requires significant efforts to (i) identify new therapeutic
      strategies able to control the evolution of dysimmune encephalitis and refractory status
      epilepticus, (ii) to identify their etiologies and (iii) to propose neuroprotective
      strategies.

      Therefore, the investigators will organize a collection of biological samples (blood,
      cerebrospinal fluid, post-mortem brain tissues) and paraclinical data (electroencephalogram,
      evoked potential, CT, MRI) in patients with severe epilepsies, whether or not associated with
      autoantibodies, and/or evolving into status epilepticus.

      This study should bring new insights allowing to better understand mechanisms that trigger
      the emergence of an epileptic brain (epileptogenesis) through :

      (i) the identification and characterization of new pathophysiological pathways involving
      autoimmunity directed against the cerebral cortex and associated with severe epilepsy (ii)
      the identification and characterization of pathophysiological pathways participating in the
      excitotoxicity observed in status epilepticus.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Identification of (i) antibodies in the plasma and in the cerebrospinal fluid of patients with dysimmune encephalitis and (ii) biomarkers for neuronal death in the plasma and in the cerebrospinal fluid of patients with status epilepticus
time frame: 9 months
description: Looking for antibodies with cell-based binding assay or monospecific recombinant assay. Identification of biomarkers for neuronal death with electrochemiluminometric sandwich immunoassays (Kryptor and ModularE170, Roche Diagnostic)
measure: Identification of new dysimmune abnormalities
time frame: 9 months
description: Lymphocyte phenotyping, cytokines quantification
measure: Identification of specific EEG patterns associated to dysimmune encephalitis and/or status epilepticus
time frame: 9 months
description: EEG signals will be reviewed and classifiyed according to a EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs)
measure: Identification of new genetic pathways associated to dysimmune encephalitis and status
time frame: 9 months
description: Genetic biomarkers
measure: Identification of new metabolic pathway that may participate in the excitotoxicity observed in status epilepticus or dysimmune encephalitis
time frame: 9 months
description: Looking for diagnostic and prognosis biomarkers. Characterization of the brain cholesterol homeostasis with UPLC-MS/MS method and enzymatic assays. Evaluation of new biomarkers (proteins, lipids, genes).
arm group label: Group 1 : Status epilepticus
arm group type: Other
arm group label: Group 2 : Dysimmune encephalitis
arm group type: Other
arm group label: Group 3 : Control patients
arm group type: Other
intervention type: Other
intervention name: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)
description: Collection of biological samples and clinical/paraclinical data
arm group label: Group 1 : Status epilepticus
arm group label: Group 2 : Dysimmune encephalitis
arm group label: Group 3 : Control patients
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: No
last name: Vincent NAVARRO, Pr
role: Principal Investigator
affiliation: Hôpital Pitié Salpêtrière - Assitance Publique Hôpitaux de Paris
last name: Vincent NAVARRO, Pr
phone: 01 42 16 19 40
email: vincent.navarro@aphp.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Brain Diseases
mesh term: Encephalitis
mesh term: Status Epilepticus