<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/NCT04451135</url>
  </required_header>
  <id_info>
    <org_study_id>202006108</org_study_id>
    <nct_id>NCT04451135</nct_id>
  </id_info>
  <brief_title>CET- REM (Correlating ECT Response to EEG Markers)</brief_title>
  <official_title>Correlating Electroconvulsive Therapy Response to Electroencephalographic Ictal Complexes and Postictal Markers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</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>
      Single-center study to determine the relationship between changes in depression symptoms and&#xD;
      electroencephalographic (EEG) patterns induced by electroconvulsive therapy (ECT)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Electroconvulsive therapy (ECT) is an effective treatment for many psychiatric illnesses,&#xD;
      including major depressive disorder. While effective, objective markers have not been&#xD;
      developed to predict clinical outcome trajectories following ECT. This is important given the&#xD;
      risks and costs incurred during a full treatment course. Electroencephalography (EEG) is&#xD;
      typically employed to monitor the generation and termination of ECT-induced seizures but&#xD;
      leverage of markers toward prognostication remains a future goal. The investigators have&#xD;
      characterized two distinct EEG patterns associated with ECT-induced generalized seizures and&#xD;
      have two sleep markers that may serve as markers for predicting response to treatment.&#xD;
      Central Positive Complexes (CPCs) are large ictal complexes with a scalp topology of voltage&#xD;
      declining from the top of the head. CPCs are localized to cortical areas that are involved in&#xD;
      the formation of sleep spindles and slow wave sleep. A pattern of low-voltage activity, known&#xD;
      as post-ictal generalized electroencephalographic suppression (PGES), is frequently used to&#xD;
      document termination of these seizures. Additionally, two EEG markers of sleep microstructure&#xD;
      may have utility given their association with synaptic plasticity, a process presumably&#xD;
      invoked over the course of ECT-induced recovery from psychiatric illness as pathologic neural&#xD;
      circuitry undergoes reconfiguration. These two markers, sleep spindles and slow waves show&#xD;
      altered expression patterns in patients with psychiatric disorders, and thus may be useful as&#xD;
      objective markers of ECT responsiveness. None of the above EEG markers have been explored for&#xD;
      an association to interval changes in disease severity over the course of ECT. This project&#xD;
      will incisively probe the relationships between temporal trajectories of major depressive&#xD;
      disorder severity and longitudinal measurements of ictal and postictal EEG markers. Ninety&#xD;
      patients will be followed for up to 22 ECT sessions. Bedside clinical instruments will allow&#xD;
      assessments of depression severity. High-density (65-electrode) EEG caps will be acquired&#xD;
      before and up to 30 minutes following ECT electrical stimulation. Duration of CPCs will be&#xD;
      determined using a novel automated algorithm. Duration of PGES will be evaluated using&#xD;
      recently validated automated algorithms. Wireless wearable devices will address previous&#xD;
      barriers to the longitudinal study of sleep microstructure in the outpatient ECT setting.&#xD;
      Slow wave activity and density of sleep spindles will be evaluated at the first cycle of N3&#xD;
      and N2 sleep, respectively. For a subset of patients, feasibility will be assessed for the&#xD;
      potentiation of slow wave activity through closed loop acoustic stimulation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 9, 2020</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2024</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Interval change in Quick Inventory of Depressive Symptomatology-16 Item Self Report (QIDS-SR16) between ECT sessions.</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>16 item Self-report questionnaire that best describes the participant's depressive symptoms over the last seven days. Scale: 0=never or do not, 3=nearly all the time, or the highest level of time listed on the question.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>Questions relating to usual sleep habits during the past month. The first four questions are free text entry and indicate the patient's sleep experience for the majority of days and nights in the past month. The remaining questions are on a scale with 1=not during the past month, 2=less than once a week, 3=Once or twice a week, 4=Three or more times a week</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Central Positive Complexes during ECT treatments.</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>Total time (in seconds) during the ictal period for which CPCs are present in the EEG immediately following seizure induction until termination of the seizure.&#xD;
Range of values: 0 - 300 seconds</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of PGES during ECT treatments.</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>Total time (in seconds) during the postictal period for which PGES is present in the EEG immediately following seizure termination for up to 5 minutes.&#xD;
Range of values: 0 - 300 seconds</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Amplitude of PGES during ECT treatments.</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>Median rectified EEG amplitude (in microvolt) during the postictal period for which PGES is present in the EEG immediately following seizure termination for up to 5 minutes.&#xD;
Range of values: 0 - 10 microvolt</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Density of EEG sleep spindles during first cycle of non-rapid eye movement (NREM) stages N2 on evenings following ECT treatments.</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>The total number of EEG sleep spindles per minute present during the first identified cycle of N2 sleep.&#xD;
Range of values: 0 - 60 spindles/min</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Slow wave activity (SWA) during first cycle of N3 sleep on evenings following ECT treatments</measure>
    <time_frame>Up to 8 weeks during patients ECT treatment course</time_frame>
    <description>Total power of EEG slow waves per minute present during the first identified cycle of N3 sleep Range of values: 0 - 50 dB/min</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>ECT</condition>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Electroencephalographic (EEG)</intervention_name>
    <description>EEG on nights after ECT session will be recorded using the DREEM device. Sleep EEG data will also be acquired for a minimum of one night prior to the first ECT session, providing a true baseline measure. The DREEM device allows continuous recording of multichannel EEG</description>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Closed loop acoustic stimulation (CLAS)</intervention_name>
    <description>Closed loop acoustic stimulation will be enabled on the DREEM headband on a subset of study participants. The device delivers stimulation in phase with the upstroke of the EEG slow wave (STIM) to boost slow oscillation activity. The timing of this stimulus augments the expression of subsequent slow waves.</description>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16)</intervention_name>
    <description>The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) is a measure of depression symptom severity that has been validated for clinical and research use53. It is a standard self-report measurement completed by patients prior to each ECT session</description>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Ictal Electroencephalographic (EEG) Measurements</intervention_name>
    <description>A high-density 65-electrode EEG scalp electrode net (EGI/Philips) with Elefix conductive gel injected within Ag/AgCl electrode sensors is utilized to monitor brain activity during the ictal period</description>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Post-Ictal Electroencephalographic (EEG) Suppression Measurements</intervention_name>
    <description>A board-certified epileptologist will review all seizures to assess seizure parameters, including duration of seizure and interval of PGES. Preprocessing of the PGES periods will be accomplished with band-pass filtering from 2 to 30 Hz with 1st order Butterworth filters.</description>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Quantitative Measurements of Sleep Microstructure</intervention_name>
    <description>Following EEG preprocessing of DREEM sleep recordings, SWA will be quantified using a custom-written MATLAB module as the average of total power spectral estimates within the 0.5-4 Hz frequency band in one minute intervals, during the first cycle of N3 sleep.</description>
    <arm_group_label>Patients with Treatment-Resistant Depression</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or greater&#xD;
&#xD;
          -  Referral for ECT index course for treatment-resistant depression (unipolar major&#xD;
             depressive disorder or bipolar depression), major depressive disorder with psychotic&#xD;
             symptoms, schizophrenia or schizoaffective being treated for a depressed episode,&#xD;
             unspecified depression&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Schizophrenia or schizoaffective disorder not being treated for a depressed episode.&#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>MohammadMehdi Kafashan, PHD</last_name>
    <phone>314-273-8848</phone>
    <email>kafashan@wustl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Orlandrea Hyche</last_name>
    <phone>314-273-1352</phone>
    <email>ohyche@wustl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Washington University School of Medicine/Barnes-Jewish Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Orlandrea Hyche</last_name>
      <phone>314-273-1352</phone>
      <email>ohyche@wustl.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lopez J, Hoffmann R, Armitage R. Reduced sleep spindle activity in early-onset and elevated risk for depression. J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):934-43. doi: 10.1016/j.jaac.2010.05.014. Epub 2010 Jul 24.</citation>
    <PMID>20732629</PMID>
  </reference>
  <reference>
    <citation>Kho KH, van Vreeswijk MF, Simpson S, Zwinderman AH. A meta-analysis of electroconvulsive therapy efficacy in depression. J ECT. 2003 Sep;19(3):139-47. doi: 10.1097/00124509-200309000-00005.</citation>
    <PMID>12972983</PMID>
  </reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>June 14, 2022</last_update_submitted>
  <last_update_submitted_qc>June 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>MohammadMehdi Kafashan</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder, Treatment-Resistant</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/NCT04451135
org study id: 202006108
nct id: NCT04451135
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Single-center study to determine the relationship between changes in depression symptoms and
      electroencephalographic (EEG) patterns induced by electroconvulsive therapy (ECT)
Electroconvulsive therapy (ECT) is an effective treatment for many psychiatric illnesses,
      including major depressive disorder. While effective, objective markers have not been
      developed to predict clinical outcome trajectories following ECT. This is important given the
      risks and costs incurred during a full treatment course. Electroencephalography (EEG) is
      typically employed to monitor the generation and termination of ECT-induced seizures but
      leverage of markers toward prognostication remains a future goal. The investigators have
      characterized two distinct EEG patterns associated with ECT-induced generalized seizures and
      have two sleep markers that may serve as markers for predicting response to treatment.
      Central Positive Complexes (CPCs) are large ictal complexes with a scalp topology of voltage
      declining from the top of the head. CPCs are localized to cortical areas that are involved in
      the formation of sleep spindles and slow wave sleep. A pattern of low-voltage activity, known
      as post-ictal generalized electroencephalographic suppression (PGES), is frequently used to
      document termination of these seizures. Additionally, two EEG markers of sleep microstructure
      may have utility given their association with synaptic plasticity, a process presumably
      invoked over the course of ECT-induced recovery from psychiatric illness as pathologic neural
      circuitry undergoes reconfiguration. These two markers, sleep spindles and slow waves show
      altered expression patterns in patients with psychiatric disorders, and thus may be useful as
      objective markers of ECT responsiveness. None of the above EEG markers have been explored for
      an association to interval changes in disease severity over the course of ECT. This project
      will incisively probe the relationships between temporal trajectories of major depressive
      disorder severity and longitudinal measurements of ictal and postictal EEG markers. Ninety
      patients will be followed for up to 22 ECT sessions. Bedside clinical instruments will allow
      assessments of depression severity. High-density (65-electrode) EEG caps will be acquired
      before and up to 30 minutes following ECT electrical stimulation. Duration of CPCs will be
      determined using a novel automated algorithm. Duration of PGES will be evaluated using
      recently validated automated algorithms. Wireless wearable devices will address previous
      barriers to the longitudinal study of sleep microstructure in the outpatient ECT setting.
      Slow wave activity and density of sleep spindles will be evaluated at the first cycle of N3
      and N2 sleep, respectively. For a subset of patients, feasibility will be assessed for the
      potentiation of slow wave activity through closed loop acoustic stimulation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Interval change in Quick Inventory of Depressive Symptomatology-16 Item Self Report (QIDS-SR16) between ECT sessions.
time frame: Up to 8 weeks during patients ECT treatment course
description: 16 item Self-report questionnaire that best describes the participant's depressive symptoms over the last seven days. Scale: 0=never or do not, 3=nearly all the time, or the highest level of time listed on the question.
measure: Pittsburgh Sleep Quality Index (PSQI)
time frame: Up to 8 weeks during patients ECT treatment course
description: Questions relating to usual sleep habits during the past month. The first four questions are free text entry and indicate the patient's sleep experience for the majority of days and nights in the past month. The remaining questions are on a scale with 1=not during the past month, 2=less than once a week, 3=Once or twice a week, 4=Three or more times a week
measure: Duration of Central Positive Complexes during ECT treatments.
time frame: Up to 8 weeks during patients ECT treatment course
description: Total time (in seconds) during the ictal period for which CPCs are present in the EEG immediately following seizure induction until termination of the seizure.
Range of values: 0 - 300 seconds
measure: Duration of PGES during ECT treatments.
time frame: Up to 8 weeks during patients ECT treatment course
description: Total time (in seconds) during the postictal period for which PGES is present in the EEG immediately following seizure termination for up to 5 minutes.
Range of values: 0 - 300 seconds
measure: Amplitude of PGES during ECT treatments.
time frame: Up to 8 weeks during patients ECT treatment course
description: Median rectified EEG amplitude (in microvolt) during the postictal period for which PGES is present in the EEG immediately following seizure termination for up to 5 minutes.
Range of values: 0 - 10 microvolt
measure: Density of EEG sleep spindles during first cycle of non-rapid eye movement (NREM) stages N2 on evenings following ECT treatments.
time frame: Up to 8 weeks during patients ECT treatment course
description: The total number of EEG sleep spindles per minute present during the first identified cycle of N2 sleep.
Range of values: 0 - 60 spindles/min
measure: Slow wave activity (SWA) during first cycle of N3 sleep on evenings following ECT treatments
time frame: Up to 8 weeks during patients ECT treatment course
description: Total power of EEG slow waves per minute present during the first identified cycle of N3 sleep Range of values: 0 - 50 dB/min
arm group label: Patients with Treatment-Resistant Depression
arm group type: Experimental
intervention type: Diagnostic Test
intervention name: Electroencephalographic (EEG)
description: EEG on nights after ECT session will be recorded using the DREEM device. Sleep EEG data will also be acquired for a minimum of one night prior to the first ECT session, providing a true baseline measure. The DREEM device allows continuous recording of multichannel EEG
arm group label: Patients with Treatment-Resistant Depression
intervention type: Diagnostic Test
intervention name: Closed loop acoustic stimulation (CLAS)
description: Closed loop acoustic stimulation will be enabled on the DREEM headband on a subset of study participants. The device delivers stimulation in phase with the upstroke of the EEG slow wave (STIM) to boost slow oscillation activity. The timing of this stimulus augments the expression of subsequent slow waves.
arm group label: Patients with Treatment-Resistant Depression
intervention type: Diagnostic Test
intervention name: Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16)
description: The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) is a measure of depression symptom severity that has been validated for clinical and research use53. It is a standard self-report measurement completed by patients prior to each ECT session
arm group label: Patients with Treatment-Resistant Depression
intervention type: Diagnostic Test
intervention name: Ictal Electroencephalographic (EEG) Measurements
description: A high-density 65-electrode EEG scalp electrode net (EGI/Philips) with Elefix conductive gel injected within Ag/AgCl electrode sensors is utilized to monitor brain activity during the ictal period
arm group label: Patients with Treatment-Resistant Depression
intervention type: Diagnostic Test
intervention name: Post-Ictal Electroencephalographic (EEG) Suppression Measurements
description: A board-certified epileptologist will review all seizures to assess seizure parameters, including duration of seizure and interval of PGES. Preprocessing of the PGES periods will be accomplished with band-pass filtering from 2 to 30 Hz with 1st order Butterworth filters.
arm group label: Patients with Treatment-Resistant Depression
intervention type: Diagnostic Test
intervention name: Quantitative Measurements of Sleep Microstructure
description: Following EEG preprocessing of DREEM sleep recordings, SWA will be quantified using a custom-written MATLAB module as the average of total power spectral estimates within the 0.5-4 Hz frequency band in one minute intervals, during the first cycle of N3 sleep.
arm group label: Patients with Treatment-Resistant Depression
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: MohammadMehdi Kafashan, PHD
phone: 314-273-8848
email: kafashan@wustl.edu
last name: Orlandrea Hyche
phone: 314-273-1352
email: ohyche@wustl.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Lopez J, Hoffmann R, Armitage R. Reduced sleep spindle activity in early-onset and elevated risk for depression. J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):934-43. doi: 10.1016/j.jaac.2010.05.014. Epub 2010 Jul 24.
PMID: 20732629
citation: Kho KH, van Vreeswijk MF, Simpson S, Zwinderman AH. A meta-analysis of electroconvulsive therapy efficacy in depression. J ECT. 2003 Sep;19(3):139-47. doi: 10.1097/00124509-200309000-00005.
PMID: 12972983
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: MohammadMehdi Kafashan
investigator title: Principal Investigator
mesh term: Depressive Disorder, Treatment-Resistant