<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/NCT04444648</url>
  </required_header>
  <id_info>
    <org_study_id>FR2</org_study_id>
    <nct_id>NCT04444648</nct_id>
  </id_info>
  <brief_title>Fluctuation of Rhymicity to Predict Recovery</brief_title>
  <acronym>FR2</acronym>
  <official_title>Longitudinal Evaluation of Circadian and Ultradian Rhythmic Fluctuations Measured by Continuous EEG During Coma to Predict the Recovery of Consciousness</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      BRIEF SUMMARY :&#xD;
&#xD;
      In the most severe cases of brain injuries, intensive care may allow patients with altered&#xD;
      consciousness to survive despite a significant risk of heavy sequelae. Persistent impairments&#xD;
      of consciousness are currently categorized according to behavior in three main neurological&#xD;
      categories: comatose state, vegetative state (recently named unresponsive wakefulness&#xD;
      syndrome) and minimally conscious state. Refining the diagnosis of internal state is a major&#xD;
      goal to determine the abilities for an optimal recovery of cognitive deficit. Circadian&#xD;
      rhythms are implicated in the regulation of sleep-wake cycles but also in cognitive&#xD;
      functions. Their role is actually revaluated in the mechanisms of consciousness impairment.&#xD;
      First, it is well known that cognitive performances partially depend on such rhythms as they&#xD;
      are more elevated during the day and correlated to the hormonal secretion. In a prognostic&#xD;
      point of view, fewer rhythmic perturbations during the initial resuscitation period (with&#xD;
      reorganized sleep rhythms and the presence of paradoxical sleep) could be associated to a&#xD;
      higher functional outcome.&#xD;
&#xD;
      However, this internal state of alertness could be highly variable during the day as it might&#xD;
      be influenced by specific rhythms such as the circadian rhythm. Only a continuous assessment&#xD;
      could help defining them properly.&#xD;
&#xD;
      Thus, investigators hypothesize that the circadian restauration, assessed in a dynamic&#xD;
      perspective, is associated with the improvement of content and level of awareness. The main&#xD;
      challenge of our study is to capture the long-term changes in the evolution of circadian and&#xD;
      ultradian rhythms and to keep a part of the natural history of the clinical recovery of these&#xD;
      patients.&#xD;
&#xD;
      To achieve this goal, the investigators plan to analyze during more than 2 days both&#xD;
      neurophysiological rhythms (EEG) and behavioral rhythms of alertness (&quot;Eyes&quot; scale from of&#xD;
      the Glasgow coma scale) in a dataset collected retrospectively from the population of&#xD;
      patients continuously monitored by EEG for medical purposes (to identify seizures and prevent&#xD;
      status epilepticus) in an intensive care unit of teaching hospital as far as acquisitions&#xD;
      last more than 48h and present no prolonged epileptic discharges or artifacts leading to&#xD;
      uninterpretable EGG.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 24, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">January 24, 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>Status of awakening at the end of the period in the hospital</measure>
    <time_frame>We analyze data obtained in a period between 2014 to 2017. The analysis is made since January 2020.</time_frame>
    <description>The final outcome to assess the respective predictive value of behavioural assessment in ICU and EEG assessment of circadian and ultradian rhythms will be obtained by the medical record when the patient leave the hospital using a unique functional scale, namely the GOSE (Glasgow Outcome Scale - Extended).&#xD;
We use the Glasgow coma recovery scale for assessment of behavior to check the variation of wakefulness. The scale was performed by the nursing staff every 2 to 8 hours depending on the severity of the medical condition.&#xD;
The continuous analysis of neurophysiologic data was based on EEG with a bipolar montage composed of the less noisy electrodes per recording period.&#xD;
The patient outcome at the ICU and hospital discharges were collected from the medical files.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Coma</condition>
  <arm_group>
    <arm_group_label>One groupe without distinction of age, sexe, and pathology.</arm_group_label>
    <description>Patients with strok in coma, with or without wake up, and with disorder of consciousness. No limit in age (maybe give the younger age).&#xD;
We obtain this data from medical record. Every assessment was made of clinical purposes.&#xD;
We use the Glasgow coma recovery scale for assessment of behavior to check the variation of wakefulness. The scale was performed by the nursing staff every 2 to 8 hours depending on the severity of the medical condition.&#xD;
The continuous analysis of neurophysiologic data was based on EEG with a bipolar montage composed of the less noisy electrodes per recording period.&#xD;
The EEG features will include: spectral analysis (relative and absolute power in 4 canonical bands: Delta/Theta/Alpha/Beta) and complexity analysis (DFA, determinism, SVD entropy and permutation entropy).&#xD;
The patient outcome at the ICU and hospital discharges were collected from the medical files.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>No intervention</description>
    <arm_group_label>One groupe without distinction of age, sexe, and pathology.</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Comatose patient in ICU under intermittent behavioural evaluation and continuous EEG&#xD;
        recording.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patient&#xD;
&#xD;
          -  Admitted in ICU&#xD;
&#xD;
          -  Altered level of consciousness not explained by a continuous sedation&#xD;
&#xD;
          -  EEG during more than 48h consecutively&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prolonged epileptic discharges leading to uninterpretable EEG rhythms&#xD;
&#xD;
          -  Prolonged artifacts leading to uninterpretable EEG trace&#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_contact>
    <last_name>Florent GOBERT</last_name>
    <phone>0472681296</phone>
    <email>florent.gobert01@chu-lyon.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Lyon teaching hospital, Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florent GOBERT</last_name>
      <phone>0472681296</phone>
      <email>florent.gobert01@chu-lyon.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</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>Coma</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/NCT04444648
org study id: FR2
nct id: NCT04444648
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
BRIEF SUMMARY :

      In the most severe cases of brain injuries, intensive care may allow patients with altered
      consciousness to survive despite a significant risk of heavy sequelae. Persistent impairments
      of consciousness are currently categorized according to behavior in three main neurological
      categories: comatose state, vegetative state (recently named unresponsive wakefulness
      syndrome) and minimally conscious state. Refining the diagnosis of internal state is a major
      goal to determine the abilities for an optimal recovery of cognitive deficit. Circadian
      rhythms are implicated in the regulation of sleep-wake cycles but also in cognitive
      functions. Their role is actually revaluated in the mechanisms of consciousness impairment.
      First, it is well known that cognitive performances partially depend on such rhythms as they
      are more elevated during the day and correlated to the hormonal secretion. In a prognostic
      point of view, fewer rhythmic perturbations during the initial resuscitation period (with
      reorganized sleep rhythms and the presence of paradoxical sleep) could be associated to a
      higher functional outcome.

      However, this internal state of alertness could be highly variable during the day as it might
      be influenced by specific rhythms such as the circadian rhythm. Only a continuous assessment
      could help defining them properly.

      Thus, investigators hypothesize that the circadian restauration, assessed in a dynamic
      perspective, is associated with the improvement of content and level of awareness. The main
      challenge of our study is to capture the long-term changes in the evolution of circadian and
      ultradian rhythms and to keep a part of the natural history of the clinical recovery of these
      patients.

      To achieve this goal, the investigators plan to analyze during more than 2 days both
      neurophysiological rhythms (EEG) and behavioral rhythms of alertness ("Eyes" scale from of
      the Glasgow coma scale) in a dataset collected retrospectively from the population of
      patients continuously monitored by EEG for medical purposes (to identify seizures and prevent
      status epilepticus) in an intensive care unit of teaching hospital as far as acquisitions
      last more than 48h and present no prolonged epileptic discharges or artifacts leading to
      uninterpretable EGG.
observational model: Cohort
time perspective: Retrospective
measure: Status of awakening at the end of the period in the hospital
time frame: We analyze data obtained in a period between 2014 to 2017. The analysis is made since January 2020.
description: The final outcome to assess the respective predictive value of behavioural assessment in ICU and EEG assessment of circadian and ultradian rhythms will be obtained by the medical record when the patient leave the hospital using a unique functional scale, namely the GOSE (Glasgow Outcome Scale - Extended).
We use the Glasgow coma recovery scale for assessment of behavior to check the variation of wakefulness. The scale was performed by the nursing staff every 2 to 8 hours depending on the severity of the medical condition.
The continuous analysis of neurophysiologic data was based on EEG with a bipolar montage composed of the less noisy electrodes per recording period.
The patient outcome at the ICU and hospital discharges were collected from the medical files.
arm group label: One groupe without distinction of age, sexe, and pathology.
description: Patients with strok in coma, with or without wake up, and with disorder of consciousness. No limit in age (maybe give the younger age).
We obtain this data from medical record. Every assessment was made of clinical purposes.
We use the Glasgow coma recovery scale for assessment of behavior to check the variation of wakefulness. The scale was performed by the nursing staff every 2 to 8 hours depending on the severity of the medical condition.
The continuous analysis of neurophysiologic data was based on EEG with a bipolar montage composed of the less noisy electrodes per recording period.
The EEG features will include: spectral analysis (relative and absolute power in 4 canonical bands: Delta/Theta/Alpha/Beta) and complexity analysis (DFA, determinism, SVD entropy and permutation entropy).
The patient outcome at the ICU and hospital discharges were collected from the medical files.
intervention type: Combination Product
intervention name: No intervention
description: No intervention
arm group label: One groupe without distinction of age, sexe, and pathology.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Florent GOBERT
phone: 0472681296
email: florent.gobert01@chu-lyon.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Coma