<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/NCT04405986</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2020/20</org_study_id>
    <nct_id>NCT04405986</nct_id>
  </id_info>
  <brief_title>Exploring Brain Damages After COVID-19 Infection</brief_title>
  <acronym>BRAINCOV</acronym>
  <official_title>Exploring Brain Damages After COVID-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Bordeaux</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>
      Although direct evidence is currently lacking, the high identity between SARS-CoV-1 and&#xD;
      SARS-CoV-2 suggests, that the latter viral strain could also infect the Central Nervous&#xD;
      System (CNS). Indeed, some cases of SARS-COV2 encephalitis begin to be described and CNS&#xD;
      damages are increasingly highlighted in the literature, but still not objectified by imaging&#xD;
      and do not allow to explain the entire clinical patterns. We hypothesise that these CNS&#xD;
      damages are not always objectified by Magnetic Resonance Imaging (MRI) but could be&#xD;
      indirectly observed by a physiological dysfunction of neural conduction in the brainstem. We&#xD;
      will explore brainstem disruption through an electrophysiological approach.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Clinical and preclinical data from studies with other coronaviruses suggest an evident&#xD;
      neurotropism, which may result in more complex clinical scenarios. Can the SARS-CoV-2 enter&#xD;
      the Central Nervous System (CNS) and infect neural cells ? And if yes, how the CNS damage&#xD;
      contributes to pathophysiology of the COVID-19, to its signs, symptoms and progression as&#xD;
      well as to its sequelae. It has been demonstrated that coronaviruses such as SARS-CoV and&#xD;
      MERS-CoV do not limit their presence to the respiratory tract and frequently invade the CNS.&#xD;
      The intranasal administration of SARS-CoV-1 or MERS-COV resulted in the rapid invasion of&#xD;
      viral particles into the brain of mice, possibly through the olfactory bulb via&#xD;
      trans-synaptic route. The brainstem, which hosts the respiratory neuronal circuit in the&#xD;
      medulla, was severely infected with both types of viruses, which may contribute to&#xD;
      degradation and failure of respiratory centres.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 19, 2020</start_date>
  <completion_date type="Actual">March 10, 2021</completion_date>
  <primary_completion_date type="Actual">March 10, 2021</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>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Latency of electrophysiological response</measure>
    <time_frame>Inclusion (T0)</time_frame>
    <description>Latencies of electrophysiological responses with Auditory Evoked Potentials</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Delay of Muscle contraction</measure>
    <time_frame>Inclusion (T0)</time_frame>
    <description>Delay of Muscle contraction (Blink reflex)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Delay of silent period</measure>
    <time_frame>Inclusion (T0)</time_frame>
    <description>Delay of silent period while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of silent period</measure>
    <time_frame>Inclusion (T0)</time_frame>
    <description>Duration of silent period while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Inhibition rate</measure>
    <time_frame>Inclusion (T0)</time_frame>
    <description>Inhibition rate while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>SARS-CoV 2</condition>
  <arm_group>
    <arm_group_label>Electrophysiological procedure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brainstem reflexes and neural conduction will be explored using Auditory Evoked Potentials (AEP) and blink and Masseter Inhibitory Reflex (MIR) in hospitalised patients with COVID infection</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Auditory Evoked Potentials (AEP)</intervention_name>
    <description>Record of electrophysiological responses (Auditory Evoked Potentials or AEP) during auditory stimulations with an electroencephalogram (EEG).</description>
    <arm_group_label>Electrophysiological procedure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blink and Masseter Inhibitory Reflex</intervention_name>
    <description>Electrophysiological exploration while stimulating trigeminal nerve to record 1) motor response induced (muscle contraction delay (Blink)) of the facial nerve, or 2) the contraction inhibition of masseters (Masseter Inhibitory Reflex (MIR)).</description>
    <arm_group_label>Electrophysiological procedure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria :&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Hospitalized patient suffering from a positive COVID 19 diagnosed by Reverse&#xD;
             transcription polymerase chain reaction (RT-PCR) or chest computed tomography scan&#xD;
             (CTscan) with specific lesions&#xD;
&#xD;
        Exclusion Criteria :&#xD;
&#xD;
          -  History of neurological damage interfering with auditory evoked potentials (PEA) and&#xD;
             Electromyography (EMG) reflexes of the brainstem (stroke of the brainstem, acoustic&#xD;
             neuroma, amyotrophic lateral sclerosis, facial diplegia, damage to nerves V or VII,&#xD;
             etc.)&#xD;
&#xD;
          -  Impaired alertness&#xD;
&#xD;
          -  Sedative treatments or treatments that disturb nerve conduction.&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Individuals under legal protection or unable to express personally their consent&#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>Bertrand Glize</last_name>
    <role>Principal Investigator</role>
    <affiliation>bertrand.glize@chu-bordeaux.fr</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <zip>33 076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>May 8, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>April 7, 2021</last_update_submitted>
  <last_update_submitted_qc>April 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Brainstem</keyword>
  <keyword>Electrophysiology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Brain Injuries</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/NCT04405986
org study id: CHUBX 2020/20
nct id: NCT04405986
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Although direct evidence is currently lacking, the high identity between SARS-CoV-1 and
      SARS-CoV-2 suggests, that the latter viral strain could also infect the Central Nervous
      System (CNS). Indeed, some cases of SARS-COV2 encephalitis begin to be described and CNS
      damages are increasingly highlighted in the literature, but still not objectified by imaging
      and do not allow to explain the entire clinical patterns. We hypothesise that these CNS
      damages are not always objectified by Magnetic Resonance Imaging (MRI) but could be
      indirectly observed by a physiological dysfunction of neural conduction in the brainstem. We
      will explore brainstem disruption through an electrophysiological approach.
Clinical and preclinical data from studies with other coronaviruses suggest an evident
      neurotropism, which may result in more complex clinical scenarios. Can the SARS-CoV-2 enter
      the Central Nervous System (CNS) and infect neural cells ? And if yes, how the CNS damage
      contributes to pathophysiology of the COVID-19, to its signs, symptoms and progression as
      well as to its sequelae. It has been demonstrated that coronaviruses such as SARS-CoV and
      MERS-CoV do not limit their presence to the respiratory tract and frequently invade the CNS.
      The intranasal administration of SARS-CoV-1 or MERS-COV resulted in the rapid invasion of
      viral particles into the brain of mice, possibly through the olfactory bulb via
      trans-synaptic route. The brainstem, which hosts the respiratory neuronal circuit in the
      medulla, was severely infected with both types of viruses, which may contribute to
      degradation and failure of respiratory centres.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Latency of electrophysiological response
time frame: Inclusion (T0)
description: Latencies of electrophysiological responses with Auditory Evoked Potentials
measure: Delay of Muscle contraction
time frame: Inclusion (T0)
description: Delay of Muscle contraction (Blink reflex)
measure: Delay of silent period
time frame: Inclusion (T0)
description: Delay of silent period while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex)
measure: Duration of silent period
time frame: Inclusion (T0)
description: Duration of silent period while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex)
measure: Inhibition rate
time frame: Inclusion (T0)
description: Inhibition rate while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex)
arm group label: Electrophysiological procedure
arm group type: Experimental
description: Brainstem reflexes and neural conduction will be explored using Auditory Evoked Potentials (AEP) and blink and Masseter Inhibitory Reflex (MIR) in hospitalised patients with COVID infection
intervention type: Procedure
intervention name: Auditory Evoked Potentials (AEP)
description: Record of electrophysiological responses (Auditory Evoked Potentials or AEP) during auditory stimulations with an electroencephalogram (EEG).
arm group label: Electrophysiological procedure
intervention type: Procedure
intervention name: Blink and Masseter Inhibitory Reflex
description: Electrophysiological exploration while stimulating trigeminal nerve to record 1) motor response induced (muscle contraction delay (Blink)) of the facial nerve, or 2) the contraction inhibition of masseters (Masseter Inhibitory Reflex (MIR)).
arm group label: Electrophysiological procedure
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bertrand Glize
role: Principal Investigator
affiliation: bertrand.glize@chu-bordeaux.fr
facility: 
country: France
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Brain Injuries