<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/NCT03268824</url>
  </required_header>
  <id_info>
    <org_study_id>VDR_2017_1</org_study_id>
    <nct_id>NCT03268824</nct_id>
  </id_info>
  <brief_title>Impact of Epileptic Discharge on the Structural Connectivity of the Developing Brain</brief_title>
  <acronym>EPITRACT</acronym>
  <official_title>Impact of Epileptic Discharge on the Structural Connectivity of the Developing Brain: Combination of Intracerebral Stereotactic Electroencephalography Recording and Diffusion Tensor Imaging in Children With Drug-resistant Focal Epilepsy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondation Ophtalmologique Adolphe de Rothschild</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondation Ophtalmologique Adolphe de Rothschild</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>
      Focal epilepsy is associated with widespread alterations in structural brain connectivity,&#xD;
      often present at the disease onset and related to learning disabilities. Whether ongoing&#xD;
      seizure activity contributes to network pathology is a matter of debate. This study intends&#xD;
      to measure the impact of seizures on structural connectivity on a local and on a global&#xD;
      level. In children examined with intracerebral electrodes to evaluate whether a surgical cure&#xD;
      can be proposed, we combine intracerebral stereotactic electroencephalography (EEG)&#xD;
      recordings with diffusion weighted imaging of white matter fibers. On the local level, the&#xD;
      study will quantify the number of deficient connections in the seizure onset zone. On a&#xD;
      global level, the study will compare the white matter fibers of the left and right hemisphere&#xD;
      to probe whether physiological language lateralization is preserved.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Drug-resistant focal epilepsy is a debilitating disease as it is often accompanied by&#xD;
      learning disabilities and behavioral disorders, that can be present at the disease onset and&#xD;
      have ample repercussions on the child's quality of life.&#xD;
&#xD;
      Despite a focal onset of seizures, the dysfunction of the cerebral networks is diffuse.&#xD;
      Structural brain connectivity can be measured with diffusion tractography, which has shown&#xD;
      evidence of widespread network pathology in focal epilepsy, probably explaining the&#xD;
      associated learning disabilities. Whether ongoing seizure activity further modifies network&#xD;
      wiring and possibly generates abnormal pathways along the routes of seizure propagation is a&#xD;
      matter of debate.&#xD;
&#xD;
      The study intends to probe the effect of seizures on cerebral connectivity, both on a local&#xD;
      and on a global level. Children who undergo presurgical evaluation to probe whether their&#xD;
      epilepsy can be cured by surgery are recorded with implanted intracerebral electrodes for&#xD;
      clinical purposes. A diffusion Magnetic Resonance Imaging will be performed prior to&#xD;
      implantation in order to relate tractography measures to seizure recordings. On the local&#xD;
      level, intracerebral electroencephalogram (EEG) will be analysed to quantify the intensity of&#xD;
      epileptic discharge (the epileptogenicity index) on each electrode contact. Loss of&#xD;
      connectivity (or disconnections) is determined with diffusion tractography for each brain&#xD;
      region. Then correlation between the degree of epileptogenicity and with the number of&#xD;
      disconnections will be studied.&#xD;
&#xD;
      On a global level, the study will quantify all white matter fibers within the language area&#xD;
      (Broca's) in the left and the corresponding area in the right hemisphere. The difference&#xD;
      between hemispheres yields us the lateralization index. The secondary outcome probes whether&#xD;
      children with focal epilepsy have atypical language organization, as a measure of diffuse&#xD;
      changes in brain wiring.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between the number of cerebral disconnections and the epileptogenicity index</measure>
    <time_frame>Baseline</time_frame>
    <description>The epileptogenicity index is based on measurement of the intensity of rapid frequency discharges in relation to the cerebral activity outside the seizures.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">82</enrollment>
  <condition>Epilepsies, Focal</condition>
  <condition>Pediatrics</condition>
  <condition>Drug Resistant Epilepsy</condition>
  <arm_group>
    <arm_group_label>Children / adolescents with drug-resistant focal epilepsy</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Children / adolescents without drug-resistant focal epilepsy</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Electroencephalogram (EEG)</intervention_name>
    <description>Intracerebral electroencephalogram (EEG) will be analysed to quantify the intensity of epileptic discharge (the epileptogenicity index) on each electrode contact (only for children with focal epilepsy).</description>
    <arm_group_label>Children / adolescents with drug-resistant focal epilepsy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Diffusion Tensor imaging</intervention_name>
    <description>We will perform Diffusion Tensor imaging in order to relate tractography measures to seizure recordings. Loss of connectivity (or disconnections) will be determined with diffusion tractography for each brain region. Then we will correlate the degree of epileptogenicity with the number of disconnections.</description>
    <arm_group_label>Children / adolescents with drug-resistant focal epilepsy</arm_group_label>
    <arm_group_label>Children / adolescents without drug-resistant focal epilepsy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Language assessment</intervention_name>
    <description>The language assessment will be adapted to the age of the child, with a predominant neuropsychological component.</description>
    <arm_group_label>Children / adolescents with drug-resistant focal epilepsy</arm_group_label>
    <arm_group_label>Children / adolescents without drug-resistant focal epilepsy</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Children/adolescents with drug resistant focal epilepsy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Drug resistant focal epilepsy&#xD;
&#xD;
        Inclusion Criteria for control patients:&#xD;
&#xD;
        - without drug resistant focal epilepsy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe mental retardation (IQ &lt; 50)&#xD;
&#xD;
          -  Lack of French-language skills&#xD;
&#xD;
          -  Contraindications to MRI&#xD;
&#xD;
          -  Bi-hemispherical epilepsy or affecting multiple lobes&#xD;
&#xD;
        Exclusion Criteria for control patients:&#xD;
&#xD;
          -  Severe mental retardation (IQ &lt; 50)&#xD;
&#xD;
          -  Lack of French-language skills&#xD;
&#xD;
          -  Contraindications to MRI&#xD;
&#xD;
          -  Congenital pathology altering cerebral connectivity&#xD;
&#xD;
          -  Parenchymal brain lesions&#xD;
&#xD;
          -  Unilateral or bilateral blindness&#xD;
&#xD;
          -  Unilateral or bilateral deafness&#xD;
&#xD;
          -  Autistic disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vera Dinkelacker, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondation Ophtalmologique A. de Rothschild</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laurence Salomon, MD PhD</last_name>
    <phone>0148036431</phone>
    <phone_ext>+33</phone_ext>
    <email>lsalomon@for.paris</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vera Dinkelacker, MD PhD</last_name>
    <phone>0148036853</phone>
    <phone_ext>+33</phone_ext>
    <email>vdinkelacker@for.paris</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fondation Ophtalmologique A. de Rothschild</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vera Dinkelacker, MD PhD</last_name>
      <phone>0148036853</phone>
      <phone_ext>+33</phone_ext>
      <email>vdinkelacker@for.paris</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>February 16, 2023</last_update_submitted>
  <last_update_submitted_qc>February 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
    <mesh_term>Epilepsies, Partial</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03268824
org study id: VDR_2017_1
nct id: NCT03268824
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Focal epilepsy is associated with widespread alterations in structural brain connectivity,
      often present at the disease onset and related to learning disabilities. Whether ongoing
      seizure activity contributes to network pathology is a matter of debate. This study intends
      to measure the impact of seizures on structural connectivity on a local and on a global
      level. In children examined with intracerebral electrodes to evaluate whether a surgical cure
      can be proposed, we combine intracerebral stereotactic electroencephalography (EEG)
      recordings with diffusion weighted imaging of white matter fibers. On the local level, the
      study will quantify the number of deficient connections in the seizure onset zone. On a
      global level, the study will compare the white matter fibers of the left and right hemisphere
      to probe whether physiological language lateralization is preserved.
Drug-resistant focal epilepsy is a debilitating disease as it is often accompanied by
      learning disabilities and behavioral disorders, that can be present at the disease onset and
      have ample repercussions on the child's quality of life.

      Despite a focal onset of seizures, the dysfunction of the cerebral networks is diffuse.
      Structural brain connectivity can be measured with diffusion tractography, which has shown
      evidence of widespread network pathology in focal epilepsy, probably explaining the
      associated learning disabilities. Whether ongoing seizure activity further modifies network
      wiring and possibly generates abnormal pathways along the routes of seizure propagation is a
      matter of debate.

      The study intends to probe the effect of seizures on cerebral connectivity, both on a local
      and on a global level. Children who undergo presurgical evaluation to probe whether their
      epilepsy can be cured by surgery are recorded with implanted intracerebral electrodes for
      clinical purposes. A diffusion Magnetic Resonance Imaging will be performed prior to
      implantation in order to relate tractography measures to seizure recordings. On the local
      level, intracerebral electroencephalogram (EEG) will be analysed to quantify the intensity of
      epileptic discharge (the epileptogenicity index) on each electrode contact. Loss of
      connectivity (or disconnections) is determined with diffusion tractography for each brain
      region. Then correlation between the degree of epileptogenicity and with the number of
      disconnections will be studied.

      On a global level, the study will quantify all white matter fibers within the language area
      (Broca's) in the left and the corresponding area in the right hemisphere. The difference
      between hemispheres yields us the lateralization index. The secondary outcome probes whether
      children with focal epilepsy have atypical language organization, as a measure of diffuse
      changes in brain wiring.
observational model: Other
time perspective: Cross-Sectional
measure: Correlation between the number of cerebral disconnections and the epileptogenicity index
time frame: Baseline
description: The epileptogenicity index is based on measurement of the intensity of rapid frequency discharges in relation to the cerebral activity outside the seizures.
arm group label: Children / adolescents with drug-resistant focal epilepsy
arm group label: Children / adolescents without drug-resistant focal epilepsy
intervention type: Device
intervention name: Electroencephalogram (EEG)
description: Intracerebral electroencephalogram (EEG) will be analysed to quantify the intensity of epileptic discharge (the epileptogenicity index) on each electrode contact (only for children with focal epilepsy).
arm group label: Children / adolescents with drug-resistant focal epilepsy
intervention type: Device
intervention name: Diffusion Tensor imaging
description: We will perform Diffusion Tensor imaging in order to relate tractography measures to seizure recordings. Loss of connectivity (or disconnections) will be determined with diffusion tractography for each brain region. Then we will correlate the degree of epileptogenicity with the number of disconnections.
arm group label: Children / adolescents with drug-resistant focal epilepsy
arm group label: Children / adolescents without drug-resistant focal epilepsy
intervention type: Other
intervention name: Language assessment
description: The language assessment will be adapted to the age of the child, with a predominant neuropsychological component.
arm group label: Children / adolescents with drug-resistant focal epilepsy
arm group label: Children / adolescents without drug-resistant focal epilepsy
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Months
maximum age: 16 Years
healthy volunteers: No
last name: Vera Dinkelacker, MD PhD
role: Principal Investigator
affiliation: Fondation Ophtalmologique A. de Rothschild
last name: Laurence Salomon, MD PhD
phone: 0148036431
phone ext: +33
email: lsalomon@for.paris
last name: Vera Dinkelacker, MD PhD
phone: 0148036853
phone ext: +33
email: vdinkelacker@for.paris
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Drug Resistant Epilepsy
mesh term: Epilepsies, Partial
sharing ipd: Undecided