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/NCT06012916</url>
    </required_header>
    <id_info>
      <org_study_id>22-0696</org_study_id>
      <nct_id>NCT06012916</nct_id>
    </id_info>
    <brief_title>Brain Network Dynamics of Depression During Esketamine Treatment</brief_title>
    <acronym>K-BRAINED</acronym>
    <official_title>Brain Network Dynamics of Depression During Esketamine Treatment</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of North Carolina, Chapel Hill</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of North Carolina, Chapel Hill</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a monocentric, observational clinical trial investigating the effect of Esketamine on&#xD;
        brain network activity and a belief updating task in people with depression. We investigate&#xD;
        the immediate and the long-term effect (approx. 8 weeks) of Esketamine on EEG signals,&#xD;
        pupillometry and belief updating and the relation of those effects on depressive&#xD;
        symptomatology.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The FDA approved the S-enantiomer of Ketamine in a nasal spray formulation (Esketamine,&#xD;
        Spravato) in 2019 for treatment resistant depression in conjunction with an oral&#xD;
        antidepressant. Albeit showing impressive short term clinical effects, the neurophysiological&#xD;
        mechanism leading to clinical improvements are not understood. The investigators aim to add&#xD;
        missing knowledge about the network dynamics of Esketamine in depression. Besides changes of&#xD;
        neural signatures, Esketamine might impact cognitive processes like belief updating.&#xD;
  &#xD;
        Previous studies have shown that people update their expectations of future life events after&#xD;
        receiving novel information. The Belief Updating Task (BUT) measures this belief update in&#xD;
        reaction to new information. Healthy individuals have been shown to update their beliefs&#xD;
        &quot;optimistically&quot;, making larger changes in their expectations in response to good news.&#xD;
        Individuals with depression lack this optimistic belief update bias. Therefore, the&#xD;
        investigators also aim to examine if Esketamine treatment reinstates the optimistic bias, how&#xD;
        those changes are mediated by neurophysiological changes during the task and if a change in&#xD;
        belief updated is related to a change of depressive symptoms.&#xD;
  &#xD;
        The first session takes place at the start of the Esketamine treatment period, whereas the&#xD;
        second experimental session is conducted closer to the end of the treatment period. In both&#xD;
        experimental sessions, EEG/pupillometry and cognitive measurements are taken before and after&#xD;
        Esketamine administration. Analyses will assess pre/post Esketamine effects within a session&#xD;
        and between two sessions.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 3, 2023</start_date>
    <completion_date type="Anticipated">January 2024</completion_date>
    <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Belief Updating in Session 1</measure>
      <time_frame>10 minutes before Esketamine application compared to 2 hours after Esketamine application</time_frame>
      <description>Participants rate the likelihood of a negative life event happening to them (E1) and their confidence in the estimate (C1). They are given a base rate (BR), described as the average lifetime probability of that event happening to someone with the same demographics. Participants will then again rate how likely the event could happen to them personally (E2).&#xD;
  Outcome variables: update = |E2 - E1| and estimation error (ER) = |E1 - BR| News: &quot;good news&quot; (BR&lt; E1) or &quot;bad news&quot; (BR&gt;E1) trials.&#xD;
  Within session relationships between update, C1, ER and covariates will be investigated using linear mixed models (LMMs) using an iterative model comparison process. The basic model will include fixed effect of News and a random intercept for individuals (id or ID).&#xD;
  Potential covariates likely include ER, C1, the Revised Life Orientation Test (LOT-R), Ketamine Side Effect Tool (KSET), and scores of depression severity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Belief Updating in Session 2</measure>
      <time_frame>10 minutes before Esketamine application compared to 2 hours after Esketamine application</time_frame>
      <description>Participants rate the likelihood of a negative life event happening to them (E1) and their confidence in the estimate (C1). They are given a base rate (BR), described as the average lifetime probability of that event happening to someone with the same demographics. Participants will then again rate how likely the event could happen to them personally (E2).&#xD;
  Outcome variables: update = |E2 - E1| and estimation error (ER) = |E1 - BR| News: &quot;good news&quot; (BR&lt; E1) or &quot;bad news&quot; (BR&gt;E1) trials.&#xD;
  Within session relationships between update, C1, ER and covariates will be investigated using linear mixed models (LMMs) using an iterative model comparison process. The basic model will include fixed effect of News and a random intercept for ID (individuals).&#xD;
  Potential covariates likely include ER, C1, the Revised Life Orientation Test (LOT-R), Ketamine Side Effect Tool (KSET), and scores of depression severity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Confidence in Beliefs Questionnaire in Session 1</measure>
      <time_frame>30 minutes before Esketamine application compared to 2 hours after Esketamine application</time_frame>
      <description>Confidence in Beliefs Questionnaire investigates the strengths of belief in statements about the participant and about someone close to them.&#xD;
  Participants rate how certain they are about each belief, higher values imply higher certainty&#xD;
  Beliefs about oneself: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line&#xD;
  Beliefs about others: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Confidence in Beliefs Questionnaire in Session 2</measure>
      <time_frame>30 minutes before Esketamine application compared to 2 hours after Esketamine application</time_frame>
      <description>Confidence in Beliefs Questionnaire investigates the strengths of belief in statements about the participant and about someone close to them.&#xD;
  Participants rate how certain they are about each belief, higher values imply higher certainty&#xD;
  Beliefs about oneself: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line&#xD;
  Beliefs about others: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Ketamine Side Effect Tool (KSET) in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application</time_frame>
      <description>Semi-structured interview to assess side effects of ketamine&#xD;
  Each item is scores from 0 (=never) to 3 (= severe) points&#xD;
  Sum scores and individual item scores can be analyzed.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Ketamine Side Effect Tool (KSET) in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application</time_frame>
      <description>Semi-structured interview to assess side effects of ketamine&#xD;
  Each item is scores from 0 (=never) to 3 (= severe) points&#xD;
  Sum scores and individual item scores can be analyzed.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Mood Likert Scale in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>Likert Scales range from 0 to 100&#xD;
  Participants make a mark on a line (left end = 0, right end = 100)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Mood Likert Scale in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>Likert Scales range from 0 to 100&#xD;
  Participants make a mark on a line (left end = 0, right end = 100)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short version (Q-LES-Q-SF)</measure>
      <time_frame>Session 1 and session 2</time_frame>
      <description>Change in Q-LES-Q-SF between Session 1 and Session 2&#xD;
  Q-LES-Q-SF is a brief, self-scoring quality of life rating scale.&#xD;
  Maximum percentage is 100%. Higher values imply higher quality of life</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Patient Health Questionnaire (PHQ-9)</measure>
      <time_frame>Session 1 and session 2</time_frame>
      <description>Change in PHQ-9 between Session 1 and Session 2&#xD;
  PHQ-9 is a brief, self-scoring depression rating scale. Higher values imply a higher depression severity.&#xD;
  Cut-off for depression is considered &gt;4 PHQ-9 points</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Hamilton Depression Rating Scale (HDRS)</measure>
      <time_frame>Session 1 and session 2</time_frame>
      <description>Change in HDRS-17 between Session 1 and Session 2&#xD;
  HDRS-17 is the most established depression rating scale. Higher values imply a higher depression severity.&#xD;
  Cut-off for depression is considered &gt;8 HDRS-17 points</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Power in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application</time_frame>
      <description>Changes in oscillatory power within an experimental session pre/post Esketamine application&#xD;
  Power will be analyzed in canonical frequency bands (e.g. alpha, beta, gamma, delta, theta)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Power in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application</time_frame>
      <description>Changes in oscillatory power within an experimental session pre/post Esketamine application&#xD;
  Power will be analyzed in canonical frequency bands (e.g. alpha, beta, gamma, delta, theta)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Connectivity in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes in functional connectivity in canonical frequency band within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Connectivity in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes in functional connectivity in canonical frequency band within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Source in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes in spatial distribution and source of electric activity in canonical frequency band within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Source in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes in spatial distribution and source of electric activity in canonical frequency band within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Aperiodic Signal in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes in slope and offset of the aperiodic EEG signal within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Aperiodic Signal in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes in slope and offset of the aperiodic EEG signal within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Entropy in Session 1</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes in after Esketamine application</time_frame>
      <description>- Changes of entropy measured in Lempel-Ziv Complexity and mutual information within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change of Resting State EEG - Entropy in Session 2</measure>
      <time_frame>5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application</time_frame>
      <description>- Changes of entropy measured in Lempel-Ziv Complexity and mutual information within an experimental session pre/post Esketamine application</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Task EEG - Event Related Potential (ERP) in Session 1</measure>
      <time_frame>30 minutes before Esketamine application and 100 minutes after Esketamine application</time_frame>
      <description>ERP after presentation of baseline will be calculated for trials with good/bad news, low/high estimation error and low/high confidence (-500 to 2000ms)&#xD;
  We will analyze the amplitude and spatial distribution of canonical ERP such as N1,N2, P3 and late positive potential</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Task EEG - Event Related Potential (ERP) in Session 2</measure>
      <time_frame>30 minutes before Esketamine application and 100 minutes after Esketamine application</time_frame>
      <description>ERP after presentation of baseline will be calculated for trials with good/bad news, low/high estimation error and low/high confidence (-500 to 2000ms)&#xD;
  We will analyze the amplitude and spatial distribution of canonical ERP such as N1,N2, P3 and late positive potential</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Task EEG - Time Frequency Analysis in Session 1</measure>
      <time_frame>30 minutes before Esketamine application and 100 minutes after Esketamine application</time_frame>
      <description>Using wavelet convolution we will conduct a time-frequency analysis for good/bad news, low/high estimation error and low/high confidence&#xD;
  Time of interest -500 to 2000ms after base rate presentation&#xD;
  Frequency of interest will be 2-40Hz</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Task EEG - Time Frequency Analysis in Session 2</measure>
      <time_frame>30 minutes before Esketamine application and 100 minutes after Esketamine application</time_frame>
      <description>Using wavelet convolution we will conduct a time-frequency analysis for good/bad news, low/high estimation error and low/high confidence&#xD;
  Time of interest -500 to 2000ms after base rate presentation&#xD;
  Frequency of interest will be 2-40 Hertz (Hz)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Pupillometry in Session 1</measure>
      <time_frame>30 minutes before Esketamine application and 100 minutes after Esketamine application</time_frame>
      <description>Pupil size during good/bad news and high/low estimation error and low/high confidence trials in the belief updating task&#xD;
  Time-locked around the presentation of the base rate (-500 to 2000ms)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Pupillometry in Session 2</measure>
      <time_frame>30 minutes before Esketamine application and 100 minutes after Esketamine application</time_frame>
      <description>Pupil size during good/bad news and high/low estimation error and low/high confidence trials in the belief updating task&#xD;
  Time-locked around the presentation of the base rate (-500 to 2000ms)</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Depressive Disorder, Major</condition>
    <arm_group>
      <arm_group_label>Treatment Resistant Depression + Esketamine Treatment</arm_group_label>
      <description>This is a group of individuals with treatment resistant depression receiving Esketamine treatment as prescribed by their physician during outpatient appointments over several weeks at the Interventional Psychiatry outpatient clinic at University of North Carolina at Chapel Hill (UNC). After signing the informed consent, electroencephalogram (EEG) will be recorded before and after Esketamine administration by the attending physician. The participant will perform a cognitive task before and after the Esketamine administration as well as complete self-scored questionnaire regarding depressive symptoms, treatment expectation and Esketamine side-effects. Clinical information like the duration of episode, medication or clinician-rated depression scores will be retrieved from the charting system.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Esketamine nasal spray</intervention_name>
      <description>This is an observational study. The Esketamine nasal spray is administered by the attending physician during a regular treatment appointment at the Interventional Psychiatry Clinic. Esketamine dosages may range between 28-84mg. The study does not interfere with the individual treatment plan in any way.</description>
      <arm_group_label>Treatment Resistant Depression + Esketamine Treatment</arm_group_label>
      <other_name>Spravato</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          The goal is to recruit individuals with an MDD diagnosis who are receiving Esketamine&#xD;
          treatment.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Major Depressive Disorder&#xD;
  &#xD;
            -  Receiving Esketamine nasal spray treatment for depression&#xD;
  &#xD;
            -  Ability to understand study procedures and sign an informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  None&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Flavio Frohlich, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of North Carolina, Chapel Hill</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tobias U Schwippel, MD</last_name>
      <phone>9199669929</phone>
      <email>tobias_schwippel@unc.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Carolina Center for Neurostimulation</name>
        <address>
          <city>Chapel Hill</city>
          <state>North Carolina</state>
          <zip>27516</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tobias U Schwippel, MD</last_name>
        <phone>919-904-5255</phone>
        <email>tobias_schwippel@unc.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Esketamine</keyword>
    <keyword>Ketamine</keyword>
    <keyword>Belief Updating</keyword>
    <keyword>Pupillometry</keyword>
    <keyword>EEG</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Depressive Disorder</mesh_term>
      <mesh_term>Depressive Disorder, Major</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Esketamine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06012916
  org study id: 22-0696
  nct id: NCT06012916
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This is a monocentric, observational clinical trial investigating the effect of Esketamine on
        brain network activity and a belief updating task in people with depression. We investigate
        the immediate and the long-term effect (approx. 8 weeks) of Esketamine on EEG signals,
        pupillometry and belief updating and the relation of those effects on depressive
        symptomatology.
  The FDA approved the S-enantiomer of Ketamine in a nasal spray formulation (Esketamine,
        Spravato) in 2019 for treatment resistant depression in conjunction with an oral
        antidepressant. Albeit showing impressive short term clinical effects, the neurophysiological
        mechanism leading to clinical improvements are not understood. The investigators aim to add
        missing knowledge about the network dynamics of Esketamine in depression. Besides changes of
        neural signatures, Esketamine might impact cognitive processes like belief updating.
  
        Previous studies have shown that people update their expectations of future life events after
        receiving novel information. The Belief Updating Task (BUT) measures this belief update in
        reaction to new information. Healthy individuals have been shown to update their beliefs
        "optimistically", making larger changes in their expectations in response to good news.
        Individuals with depression lack this optimistic belief update bias. Therefore, the
        investigators also aim to examine if Esketamine treatment reinstates the optimistic bias, how
        those changes are mediated by neurophysiological changes during the task and if a change in
        belief updated is related to a change of depressive symptoms.
  
        The first session takes place at the start of the Esketamine treatment period, whereas the
        second experimental session is conducted closer to the end of the treatment period. In both
        experimental sessions, EEG/pupillometry and cognitive measurements are taken before and after
        Esketamine administration. Analyses will assess pre/post Esketamine effects within a session
        and between two sessions.
  observational model: Case-Only
  time perspective: Prospective
  measure: Change in Belief Updating in Session 1
  time frame: 10 minutes before Esketamine application compared to 2 hours after Esketamine application
  description: Participants rate the likelihood of a negative life event happening to them (E1) and their confidence in the estimate (C1). They are given a base rate (BR), described as the average lifetime probability of that event happening to someone with the same demographics. Participants will then again rate how likely the event could happen to them personally (E2).
  Outcome variables: update = |E2 - E1| and estimation error (ER) = |E1 - BR| News: "good news" (BR< E1) or "bad news" (BR>E1) trials.
  Within session relationships between update, C1, ER and covariates will be investigated using linear mixed models (LMMs) using an iterative model comparison process. The basic model will include fixed effect of News and a random intercept for individuals (id or ID).
  Potential covariates likely include ER, C1, the Revised Life Orientation Test (LOT-R), Ketamine Side Effect Tool (KSET), and scores of depression severity.
  measure: Change in Belief Updating in Session 2
  time frame: 10 minutes before Esketamine application compared to 2 hours after Esketamine application
  description: Participants rate the likelihood of a negative life event happening to them (E1) and their confidence in the estimate (C1). They are given a base rate (BR), described as the average lifetime probability of that event happening to someone with the same demographics. Participants will then again rate how likely the event could happen to them personally (E2).
  Outcome variables: update = |E2 - E1| and estimation error (ER) = |E1 - BR| News: "good news" (BR< E1) or "bad news" (BR>E1) trials.
  Within session relationships between update, C1, ER and covariates will be investigated using linear mixed models (LMMs) using an iterative model comparison process. The basic model will include fixed effect of News and a random intercept for ID (individuals).
  Potential covariates likely include ER, C1, the Revised Life Orientation Test (LOT-R), Ketamine Side Effect Tool (KSET), and scores of depression severity.
  measure: Change in Confidence in Beliefs Questionnaire in Session 1
  time frame: 30 minutes before Esketamine application compared to 2 hours after Esketamine application
  description: Confidence in Beliefs Questionnaire investigates the strengths of belief in statements about the participant and about someone close to them.
  Participants rate how certain they are about each belief, higher values imply higher certainty
  Beliefs about oneself: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line
  Beliefs about others: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line
  measure: Change in Confidence in Beliefs Questionnaire in Session 2
  time frame: 30 minutes before Esketamine application compared to 2 hours after Esketamine application
  description: Confidence in Beliefs Questionnaire investigates the strengths of belief in statements about the participant and about someone close to them.
  Participants rate how certain they are about each belief, higher values imply higher certainty
  Beliefs about oneself: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line
  Beliefs about others: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line
  measure: Change of Ketamine Side Effect Tool (KSET) in Session 1
  time frame: 5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application
  description: Semi-structured interview to assess side effects of ketamine
  Each item is scores from 0 (=never) to 3 (= severe) points
  Sum scores and individual item scores can be analyzed.
  measure: Change of Ketamine Side Effect Tool (KSET) in Session 2
  time frame: 5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application
  description: Semi-structured interview to assess side effects of ketamine
  Each item is scores from 0 (=never) to 3 (= severe) points
  Sum scores and individual item scores can be analyzed.
  measure: Change in Mood Likert Scale in Session 1
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: Likert Scales range from 0 to 100
  Participants make a mark on a line (left end = 0, right end = 100)
  measure: Change in Mood Likert Scale in Session 2
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: Likert Scales range from 0 to 100
  Participants make a mark on a line (left end = 0, right end = 100)
  measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short version (Q-LES-Q-SF)
  time frame: Session 1 and session 2
  description: Change in Q-LES-Q-SF between Session 1 and Session 2
  Q-LES-Q-SF is a brief, self-scoring quality of life rating scale.
  Maximum percentage is 100%. Higher values imply higher quality of life
  measure: Change in Patient Health Questionnaire (PHQ-9)
  time frame: Session 1 and session 2
  description: Change in PHQ-9 between Session 1 and Session 2
  PHQ-9 is a brief, self-scoring depression rating scale. Higher values imply a higher depression severity.
  Cut-off for depression is considered >4 PHQ-9 points
  measure: Change in Hamilton Depression Rating Scale (HDRS)
  time frame: Session 1 and session 2
  description: Change in HDRS-17 between Session 1 and Session 2
  HDRS-17 is the most established depression rating scale. Higher values imply a higher depression severity.
  Cut-off for depression is considered >8 HDRS-17 points
  measure: Change of Resting State EEG - Power in Session 1
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application
  description: Changes in oscillatory power within an experimental session pre/post Esketamine application
  Power will be analyzed in canonical frequency bands (e.g. alpha, beta, gamma, delta, theta)
  measure: Change of Resting State EEG - Power in Session 2
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application
  description: Changes in oscillatory power within an experimental session pre/post Esketamine application
  Power will be analyzed in canonical frequency bands (e.g. alpha, beta, gamma, delta, theta)
  measure: Change of Resting State EEG - Connectivity in Session 1
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes in functional connectivity in canonical frequency band within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Connectivity in Session 2
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes in functional connectivity in canonical frequency band within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Source in Session 1
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes in spatial distribution and source of electric activity in canonical frequency band within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Source in Session 2
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes in spatial distribution and source of electric activity in canonical frequency band within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Aperiodic Signal in Session 1
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes in slope and offset of the aperiodic EEG signal within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Aperiodic Signal in Session 2
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes in slope and offset of the aperiodic EEG signal within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Entropy in Session 1
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes in after Esketamine application
  description: - Changes of entropy measured in Lempel-Ziv Complexity and mutual information within an experimental session pre/post Esketamine application
  measure: Change of Resting State EEG - Entropy in Session 2
  time frame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
  description: - Changes of entropy measured in Lempel-Ziv Complexity and mutual information within an experimental session pre/post Esketamine application
  measure: Change in Task EEG - Event Related Potential (ERP) in Session 1
  time frame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
  description: ERP after presentation of baseline will be calculated for trials with good/bad news, low/high estimation error and low/high confidence (-500 to 2000ms)
  We will analyze the amplitude and spatial distribution of canonical ERP such as N1,N2, P3 and late positive potential
  measure: Change in Task EEG - Event Related Potential (ERP) in Session 2
  time frame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
  description: ERP after presentation of baseline will be calculated for trials with good/bad news, low/high estimation error and low/high confidence (-500 to 2000ms)
  We will analyze the amplitude and spatial distribution of canonical ERP such as N1,N2, P3 and late positive potential
  measure: Change in Task EEG - Time Frequency Analysis in Session 1
  time frame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
  description: Using wavelet convolution we will conduct a time-frequency analysis for good/bad news, low/high estimation error and low/high confidence
  Time of interest -500 to 2000ms after base rate presentation
  Frequency of interest will be 2-40Hz
  measure: Change in Task EEG - Time Frequency Analysis in Session 2
  time frame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
  description: Using wavelet convolution we will conduct a time-frequency analysis for good/bad news, low/high estimation error and low/high confidence
  Time of interest -500 to 2000ms after base rate presentation
  Frequency of interest will be 2-40 Hertz (Hz)
  measure: Change in Pupillometry in Session 1
  time frame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
  description: Pupil size during good/bad news and high/low estimation error and low/high confidence trials in the belief updating task
  Time-locked around the presentation of the base rate (-500 to 2000ms)
  measure: Change in Pupillometry in Session 2
  time frame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
  description: Pupil size during good/bad news and high/low estimation error and low/high confidence trials in the belief updating task
  Time-locked around the presentation of the base rate (-500 to 2000ms)
  arm group label: Treatment Resistant Depression + Esketamine Treatment
  description: This is a group of individuals with treatment resistant depression receiving Esketamine treatment as prescribed by their physician during outpatient appointments over several weeks at the Interventional Psychiatry outpatient clinic at University of North Carolina at Chapel Hill (UNC). After signing the informed consent, electroencephalogram (EEG) will be recorded before and after Esketamine administration by the attending physician. The participant will perform a cognitive task before and after the Esketamine administration as well as complete self-scored questionnaire regarding depressive symptoms, treatment expectation and Esketamine side-effects. Clinical information like the duration of episode, medication or clinician-rated depression scores will be retrieved from the charting system.
  intervention type: Drug
  intervention name: Esketamine nasal spray
  description: This is an observational study. The Esketamine nasal spray is administered by the attending physician during a regular treatment appointment at the Interventional Psychiatry Clinic. Esketamine dosages may range between 28-84mg. The study does not interfere with the individual treatment plan in any way.
  arm group label: Treatment Resistant Depression + Esketamine Treatment
  other name: Spravato
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 99 Years
  healthy volunteers: No
  last name: Flavio Frohlich, PhD
  role: Principal Investigator
  affiliation: University of North Carolina, Chapel Hill
  last name: Tobias U Schwippel, MD
  phone: 9199669929
  email: tobias_schwippel@unc.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major
  mesh term: Esketamine
  sharing ipd: No