xml: <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/NCT06022055</url>
    </required_header>
    <id_info>
      <org_study_id>APHP230479</org_study_id>
      <nct_id>NCT06022055</nct_id>
    </id_info>
    <brief_title>Multimodal Study of the Human Brain Epilepsy Tissue</brief_title>
    <acronym>TIPI²</acronym>
    <official_title>Multimodal Study of the Human Brain Epilepsy Tissue</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Assistance Publique - Hôpitaux de Paris</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>ICM Co. Ltd.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Assistance Publique - Hôpitaux de Paris</source>
    <oversight_info>
      <has_dmc>Yes</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 TIPI2 study is a blood and tissue collection protocol to create an annotated&#xD;
        biorepository to support research in drug-resistant epilepsy.&#xD;
  &#xD;
        The aim of the study will be to identify new pathophysiological pathways. For this purpose,&#xD;
        the investigators will investigate with a multimodal approach blood and brain samples from&#xD;
        patients undergoing a surgery for focal drug-resistant epilepsy. The adult patients will be&#xD;
        enrolled either during the pre-surgical evaluation or right before the surgery.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study aims to investigate blood and brain samples from patients with drug-resistant&#xD;
        epilepsy in order to identify new pathophysiological biomarkers.&#xD;
  &#xD;
        The investigators will first conduct multimodal research, including:&#xD;
  &#xD;
          -  electrophysiological analyses&#xD;
  &#xD;
          -  immunohistochemistry and genetic studies&#xD;
  &#xD;
          -  biochemistry analyses&#xD;
  &#xD;
        Samples will be stored at -80°C for future research.&#xD;
  &#xD;
        Patients will undergo a follow-up evaluation within the 36 months following the surgery. New&#xD;
        clinical data and biological samples will be collected then.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2036</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2029</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>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by immuno-histological methods</measure>
      <time_frame>At the day of surgery; analyses are based on the post-operative tissues</time_frame>
      <description>The investigator will identify inflammatory cells (astrocytes, microglia, lymphocytes and neutrophil polynuclear cells) in the post-operative brain tissue, and will calculate if there is an increase of a part of these cells in the area, defined as the seizure onset zone, as compared to the non-epileptic areas.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by electrophysiological methods</measure>
      <time_frame>At the day of surgery; analyses are based on the post-operative tissues</time_frame>
      <description>The investigator will record local field potentials and neuronal firing rate from post-operative tissues, and we will research an increase of the rate of interictal epileptiform discharges and of the frequency of the neuronal firing in the seizure-onset zone, as compared to those in non-epileptic areas.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by RNA sequencing methods</measure>
      <time_frame>At the day of surgery; analyses are based on the post-operative tissues</time_frame>
      <description>The investigator will measure the expression of mRNA in cells of different parts of the post-operative brain tissue, and we will research specific expression of mRNA in the Seizure onset zone, as compared to that in other non-epileptic areas.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Identification of new pathophysiological mechanisms associated with the occurrence of a seizure : analysis of biomarkers by ELISA methods</measure>
      <time_frame>from inclusion day to 36 months after the surgery</time_frame>
      <description>The investigator will measure several proteins by Elisa, and we will define if there is a specific increase of some proteins in the sample after a seizure, as compared to the level of these proteins far from a seizure.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of biomarkers by ELISA methods</measure>
      <time_frame>from inclusion day to 36 months after the surgery</time_frame>
      <description>The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of blood cell subtypes by flow cytometry</measure>
      <time_frame>from inclusion day to 36 months after the surgery</time_frame>
      <description>The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of inflammation biomarkers by digital ultra-sensitive quantitation of proteins methods</measure>
      <time_frame>from inclusion day to 36 months after the surgery</time_frame>
      <description>The investigator will measure several inflammatory proteins including cytokines, and we will define if there is a specific increase of some proteins in the sample from epileptic patients, as compared to the level of these proteins in non-epileptic patients.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Focal Drug-resistant Epilepsy</condition>
    <arm_group>
      <arm_group_label>epileptic patients</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All patients will be enrolled in the same arm. Patients can be enrolled during the pre-surgical evaluation (group 1) or in the days preceding the surgery (group 2).</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Blood and tissue collection</intervention_name>
      <description>Blood will be collected for group 1 during (i) the enrolment visit, (ii) in the 24 hours following a seizure, (iii)before the surgery and (iv) in the 36 months following the surgery. The left-over tissue, not useful for diagnostic purpose, will be kept for research.&#xD;
  Blood will be collected for group 2 right before the surgery and in the 36 months following the surgery. The left-over tissue not useful for diagnostic purpose will be kept for research.</description>
      <arm_group_label>epileptic patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18 yo or above&#xD;
  &#xD;
            -  patients with a focal drug-resistant epilepsy&#xD;
  &#xD;
            -  patients hospitalized for a pre-surgical evaluation or for an epilepsy surgery&#xD;
  &#xD;
            -  consent obtained from the patient, or legally authorized representative&#xD;
  &#xD;
            -  affiliated to a social security system&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  None&#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>Vincent M. Navarro, MD, PHD</last_name>
      <role>Principal Investigator</role>
      <affiliation>APHP</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Vincent M. Navarro, MD, PHD</last_name>
      <phone>01 42 16 19 40</phone>
      <phone_ext>+33</phone_ext>
      <email>Vincent.navarro@aphp.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Aurélie Ms Hanin, PharmD, PhD</last_name>
      <phone>01 57 27 40 56</phone>
      <phone_ext>+33</phone_ext>
      <email>Aurelie.hanin@icm-institute.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Department of Neurology, Epilepsy Unit, Pitié-Salpêtrière Hospital</name>
        <address>
          <city>Paris</city>
          <zip>75013</zip>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Vincent M. Navarro, MD, PHD</last_name>
        <phone>01 42 16 19 40</phone>
        <phone_ext>+33</phone_ext>
        <email>Vincent.navarro@aphp.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>May 2023</verification_date>
    <study_first_submitted>May 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Focal drug-resistant epilepsy</keyword>
    <keyword>Surgery</keyword>
    <keyword>Biorepository</keyword>
    <keyword>Biomarkers</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epilepsy</mesh_term>
      <mesh_term>Drug Resistant Epilepsy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Data are available upon reasonable request&#xD;
  The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.&#xD;
  Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_time_frame>Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.</ipd_time_frame>
      <ipd_access_criteria>Researchers who provide a methodologically sound proposal.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06022055
  org study id: APHP230479
  nct id: NCT06022055
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The TIPI2 study is a blood and tissue collection protocol to create an annotated
        biorepository to support research in drug-resistant epilepsy.
  
        The aim of the study will be to identify new pathophysiological pathways. For this purpose,
        the investigators will investigate with a multimodal approach blood and brain samples from
        patients undergoing a surgery for focal drug-resistant epilepsy. The adult patients will be
        enrolled either during the pre-surgical evaluation or right before the surgery.
  This study aims to investigate blood and brain samples from patients with drug-resistant
        epilepsy in order to identify new pathophysiological biomarkers.
  
        The investigators will first conduct multimodal research, including:
  
          -  electrophysiological analyses
  
          -  immunohistochemistry and genetic studies
  
          -  biochemistry analyses
  
        Samples will be stored at -80°C for future research.
  
        Patients will undergo a follow-up evaluation within the 36 months following the surgery. New
        clinical data and biological samples will be collected then.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by immuno-histological methods
  time frame: At the day of surgery; analyses are based on the post-operative tissues
  description: The investigator will identify inflammatory cells (astrocytes, microglia, lymphocytes and neutrophil polynuclear cells) in the post-operative brain tissue, and will calculate if there is an increase of a part of these cells in the area, defined as the seizure onset zone, as compared to the non-epileptic areas.
  measure: Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by electrophysiological methods
  time frame: At the day of surgery; analyses are based on the post-operative tissues
  description: The investigator will record local field potentials and neuronal firing rate from post-operative tissues, and we will research an increase of the rate of interictal epileptiform discharges and of the frequency of the neuronal firing in the seizure-onset zone, as compared to those in non-epileptic areas.
  measure: Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by RNA sequencing methods
  time frame: At the day of surgery; analyses are based on the post-operative tissues
  description: The investigator will measure the expression of mRNA in cells of different parts of the post-operative brain tissue, and we will research specific expression of mRNA in the Seizure onset zone, as compared to that in other non-epileptic areas.
  measure: Identification of new pathophysiological mechanisms associated with the occurrence of a seizure : analysis of biomarkers by ELISA methods
  time frame: from inclusion day to 36 months after the surgery
  description: The investigator will measure several proteins by Elisa, and we will define if there is a specific increase of some proteins in the sample after a seizure, as compared to the level of these proteins far from a seizure.
  measure: Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of biomarkers by ELISA methods
  time frame: from inclusion day to 36 months after the surgery
  description: The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients.
  measure: Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of blood cell subtypes by flow cytometry
  time frame: from inclusion day to 36 months after the surgery
  description: The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients.
  measure: Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of inflammation biomarkers by digital ultra-sensitive quantitation of proteins methods
  time frame: from inclusion day to 36 months after the surgery
  description: The investigator will measure several inflammatory proteins including cytokines, and we will define if there is a specific increase of some proteins in the sample from epileptic patients, as compared to the level of these proteins in non-epileptic patients.
  arm group label: epileptic patients
  arm group type: Experimental
  description: All patients will be enrolled in the same arm. Patients can be enrolled during the pre-surgical evaluation (group 1) or in the days preceding the surgery (group 2).
  intervention type: Other
  intervention name: Blood and tissue collection
  description: Blood will be collected for group 1 during (i) the enrolment visit, (ii) in the 24 hours following a seizure, (iii)before the surgery and (iv) in the 36 months following the surgery. The left-over tissue, not useful for diagnostic purpose, will be kept for research.
  Blood will be collected for group 2 right before the surgery and in the 36 months following the surgery. The left-over tissue not useful for diagnostic purpose will be kept for research.
  arm group label: epileptic patients
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Vincent M. Navarro, MD, PHD
  role: Principal Investigator
  affiliation: APHP
  last name: Vincent M. Navarro, MD, PHD
  phone: 01 42 16 19 40
  phone ext: +33
  email: Vincent.navarro@aphp.fr
  last name: Aurélie Ms Hanin, PharmD, PhD
  phone: 01 57 27 40 56
  phone ext: +33
  email: Aurelie.hanin@icm-institute.org
  facility: 
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Epilepsy
  mesh term: Drug Resistant Epilepsy
  sharing ipd: Yes
  ipd description: Data are available upon reasonable request
  The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.
  Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
  ipd info type: Study Protocol
  ipd info type: Informed Consent Form (ICF)
  ipd time frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
  ipd access criteria: Researchers who provide a methodologically sound proposal.