<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/NCT03828604</url>
  </required_header>
  <id_info>
    <org_study_id>SIWB</org_study_id>
    <nct_id>NCT03828604</nct_id>
  </id_info>
  <brief_title>Stress-Induced Inflammation and Reward Processing</brief_title>
  <official_title>Stress-Induced Inflammation and Reward Processing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>UCLA Norman Cousins Center for Psychoneuroimmunology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</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>
      Anhedonia, or loss of interest or pleasure, is a key feature of depression and&#xD;
      transdiagnostic construct in psychopathology. Both theory and compelling evidence from&#xD;
      preclinical models implicates stress-induced inflammation as a key psychobiological pathway&#xD;
      to anhedonic behavior; however, this pathway has not been demonstrated in human models.&#xD;
      Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the&#xD;
      extent to which stress-induced inflammation alters these dimensions is unclear. The current&#xD;
      placebo controlled study used a standardized laboratory stressor task to elicit an&#xD;
      inflammatory response in a sample of a healthy young women and evaluate effects of&#xD;
      stress-induced inflammation on multiple behavioral indices of reward processing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study we propose to examine the association between psychosocial stress, the&#xD;
      stress-induced inflammatory response, and reward processing in a female undergraduate sample.&#xD;
      Specifically, we will 1) examine effects of an acute psychosocial stressor on reward&#xD;
      processing; 2) evaluate the association between stress-related changes in inflammation and&#xD;
      reward processing; and 3) test key vulnerability factors that may moderate the association&#xD;
      between stress and reward. To achieve these goals, this study will recruit 60 female&#xD;
      undergraduate students to test effects of stress on reward processing in a 3.5 hour&#xD;
      laboratory session. Participants will be randomly assigned to either experience a laboratory&#xD;
      stressor or a placebo control, and will complete reward tasks 90 minutes post stress/placebo&#xD;
      onset, at which point the peripheral inflammatory response to stress reaches its peak. The&#xD;
      reward tasks are computerized behavioral tasks that assess three domains of reward&#xD;
      processing: reward-learning, reward motivation, and reward sensitivity. Throughout the&#xD;
      session, all participants will complete self-report measures of affect and provide blood and&#xD;
      saliva samples for evaluation of the psychological and physiological stress response. Within&#xD;
      one week prior to the session, participants will attend a 1 hour visit in which they complete&#xD;
      baseline reward tasks and self-report questionnaires assessing mood, personality, early life&#xD;
      stress, and health behaviors. In total, participants will complete two visits, with a&#xD;
      duration of 4.5 hours. This study builds upon prior studies demonstrating immediate effects&#xD;
      of acute stress on reward processing, and further tests for delayed effects of acute stress&#xD;
      on reward processing. Furthermore, this will be the first study to examine inflammation as a&#xD;
      mechanism linking stress to deficits in reward processing. Findings may inform theory of&#xD;
      depression etiology and contribute to more specialized treatment that is targeted at specific&#xD;
      symptoms of depression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 12, 2017</start_date>
  <completion_date type="Actual">May 9, 2018</completion_date>
  <primary_completion_date type="Actual">December 8, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Acute Psychosocial stress vs. Non-stress active control</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Probabilistic Reward Task - Reward Responsiveness</measure>
    <time_frame>Pre-TSST/P-TSST and 90 min post-TSST/P-TSST</time_frame>
    <description>Change in the magnitude of response bias from pre to post Trier Social Stress Task (TSST) or Placebo-TSST (P-TSST).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effort Expenditure for Rewards Task - Reward Motivation</measure>
    <time_frame>Pre-TSST/P-TSST and 120 min post-TSST/P-TSST</time_frame>
    <description>Change in amount of hard trials chosen from pre to post-TSST/P-TSST (overall, and at 3 levels of probability of potential rewards; low, medium, and high)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Attentional Bias Task</measure>
    <time_frame>Pre-TSST/P-TSST and 110 min post-TSST/P-TSST</time_frame>
    <description>Change in attentional bias from pre to post-TSST/P-TSST</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effort Expenditure for Rewards Task - Reward Sensitivity</measure>
    <time_frame>120 min post-TSST</time_frame>
    <description>Strength of the relationship between changes in reward magnitude and high effort trial choice as a function of degree of change in IL-6 following acute stress</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Face Morphing Task</measure>
    <time_frame>Pre-TSST/P-TSST and 115 min post-TSST/P-TSST</time_frame>
    <description>Change in latency to detect emotional expressions</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Depressive symptoms</measure>
    <time_frame>Change in depressive symptoms from study entry to 4-month follow-up</time_frame>
    <description>The 20-item Center for Epidemiological Studies Depression Scale (CESD) is a self-report measure; participants are asked to rate how often they have experienced depressed feelings, attitudes, and behavioral symptoms during the past week (0 = rarely; 3 = most of the time). The total score range is 0 to 60, with higher scores indicating higher depressive symptoms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Affective experience during the experimental session</measure>
    <time_frame>Entry, pre-TSST/P-TSST; during TSST/P-TSST; 60, 90, 120, 150 min post TSST/P-TSST</time_frame>
    <description>Emotional reactivity and recovery from the TSST/P-TSST will be assessed using items from the Positive and Negative Affect Schedule and the Profile of Mood States. Participants rate how they feel &quot;right now (that is, at the present moment) on a 1 (very slightly or not at all) to 5 (extremely) Likert scale. Average scores for subscales are reported, including positive and negative affect (7 items each), fatigue (8 items) vigor (5 items) and confusion (7 items). Participants also use visual analogue scales (VAS) to indicate how stressed, anxious, angry, confident, calm, socially connected and happy they are currently feeling on a 0 (not at all) to 100 (extremely) scale. The VAS are completed alongside the PANAS and three additional times during the TSST/P-TSST.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Stress, Psychological</condition>
  <arm_group>
    <arm_group_label>Stress; Trier Social Stress Task</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 min challenging speech task, 5 min challenging math task; performed in front of evaluators</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Trier Social Stress Task</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5 min speech task, 5 min math task; performed alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Stress; Trier Social Stress Task</intervention_name>
    <description>Standardized acute psychosocial stressor</description>
    <arm_group_label>Stress; Trier Social Stress Task</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Placebo Trier Social Stress Task</intervention_name>
    <description>Active control version of the TSST</description>
    <arm_group_label>Placebo Trier Social Stress Task</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  English fluency&#xD;
&#xD;
          -  Age 18-28&#xD;
&#xD;
          -  Biologically female&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current illness&#xD;
&#xD;
          -  Presence or history of major medical conditions&#xD;
&#xD;
          -  Current or past diagnosis of alcohol use disorder&#xD;
&#xD;
          -  Use of tobacco&#xD;
&#xD;
          -  Use of immune-altering medications&#xD;
&#xD;
          -  Current pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>28 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chloe C Boyle, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julienne E Bower, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical and Translational Research Center, University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>February 1, 2019</last_update_submitted>
  <last_update_submitted_qc>February 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Chloe Boyle, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>reward processing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Stress, Psychological</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 31, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03828604/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03828604
org study id: SIWB
nct id: NCT03828604
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Anhedonia, or loss of interest or pleasure, is a key feature of depression and
      transdiagnostic construct in psychopathology. Both theory and compelling evidence from
      preclinical models implicates stress-induced inflammation as a key psychobiological pathway
      to anhedonic behavior; however, this pathway has not been demonstrated in human models.
      Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the
      extent to which stress-induced inflammation alters these dimensions is unclear. The current
      placebo controlled study used a standardized laboratory stressor task to elicit an
      inflammatory response in a sample of a healthy young women and evaluate effects of
      stress-induced inflammation on multiple behavioral indices of reward processing.
In this study we propose to examine the association between psychosocial stress, the
      stress-induced inflammatory response, and reward processing in a female undergraduate sample.
      Specifically, we will 1) examine effects of an acute psychosocial stressor on reward
      processing; 2) evaluate the association between stress-related changes in inflammation and
      reward processing; and 3) test key vulnerability factors that may moderate the association
      between stress and reward. To achieve these goals, this study will recruit 60 female
      undergraduate students to test effects of stress on reward processing in a 3.5 hour
      laboratory session. Participants will be randomly assigned to either experience a laboratory
      stressor or a placebo control, and will complete reward tasks 90 minutes post stress/placebo
      onset, at which point the peripheral inflammatory response to stress reaches its peak. The
      reward tasks are computerized behavioral tasks that assess three domains of reward
      processing: reward-learning, reward motivation, and reward sensitivity. Throughout the
      session, all participants will complete self-report measures of affect and provide blood and
      saliva samples for evaluation of the psychological and physiological stress response. Within
      one week prior to the session, participants will attend a 1 hour visit in which they complete
      baseline reward tasks and self-report questionnaires assessing mood, personality, early life
      stress, and health behaviors. In total, participants will complete two visits, with a
      duration of 4.5 hours. This study builds upon prior studies demonstrating immediate effects
      of acute stress on reward processing, and further tests for delayed effects of acute stress
      on reward processing. Furthermore, this will be the first study to examine inflammation as a
      mechanism linking stress to deficits in reward processing. Findings may inform theory of
      depression etiology and contribute to more specialized treatment that is targeted at specific
      symptoms of depression.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Acute Psychosocial stress vs. Non-stress active control
primary purpose: Basic Science
masking: Single (Participant)
measure: Probabilistic Reward Task - Reward Responsiveness
time frame: Pre-TSST/P-TSST and 90 min post-TSST/P-TSST
description: Change in the magnitude of response bias from pre to post Trier Social Stress Task (TSST) or Placebo-TSST (P-TSST).
measure: Effort Expenditure for Rewards Task - Reward Motivation
time frame: Pre-TSST/P-TSST and 120 min post-TSST/P-TSST
description: Change in amount of hard trials chosen from pre to post-TSST/P-TSST (overall, and at 3 levels of probability of potential rewards; low, medium, and high)
measure: Attentional Bias Task
time frame: Pre-TSST/P-TSST and 110 min post-TSST/P-TSST
description: Change in attentional bias from pre to post-TSST/P-TSST
measure: Effort Expenditure for Rewards Task - Reward Sensitivity
time frame: 120 min post-TSST
description: Strength of the relationship between changes in reward magnitude and high effort trial choice as a function of degree of change in IL-6 following acute stress
measure: Face Morphing Task
time frame: Pre-TSST/P-TSST and 115 min post-TSST/P-TSST
description: Change in latency to detect emotional expressions
measure: Depressive symptoms
time frame: Change in depressive symptoms from study entry to 4-month follow-up
description: The 20-item Center for Epidemiological Studies Depression Scale (CESD) is a self-report measure; participants are asked to rate how often they have experienced depressed feelings, attitudes, and behavioral symptoms during the past week (0 = rarely; 3 = most of the time). The total score range is 0 to 60, with higher scores indicating higher depressive symptoms.
measure: Affective experience during the experimental session
time frame: Entry, pre-TSST/P-TSST; during TSST/P-TSST; 60, 90, 120, 150 min post TSST/P-TSST
description: Emotional reactivity and recovery from the TSST/P-TSST will be assessed using items from the Positive and Negative Affect Schedule and the Profile of Mood States. Participants rate how they feel "right now (that is, at the present moment) on a 1 (very slightly or not at all) to 5 (extremely) Likert scale. Average scores for subscales are reported, including positive and negative affect (7 items each), fatigue (8 items) vigor (5 items) and confusion (7 items). Participants also use visual analogue scales (VAS) to indicate how stressed, anxious, angry, confident, calm, socially connected and happy they are currently feeling on a 0 (not at all) to 100 (extremely) scale. The VAS are completed alongside the PANAS and three additional times during the TSST/P-TSST.
arm group label: Stress; Trier Social Stress Task
arm group type: Experimental
description: 5 min challenging speech task, 5 min challenging math task; performed in front of evaluators
arm group label: Placebo Trier Social Stress Task
arm group type: Active Comparator
description: 5 min speech task, 5 min math task; performed alone
intervention type: Behavioral
intervention name: Stress; Trier Social Stress Task
description: Standardized acute psychosocial stressor
arm group label: Stress; Trier Social Stress Task
intervention type: Behavioral
intervention name: Placebo Trier Social Stress Task
description: Active control version of the TSST
arm group label: Placebo Trier Social Stress Task
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 28 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Chloe C Boyle, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Julienne E Bower, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Chloe Boyle, PhD
investigator title: Principal Investigator
mesh term: Inflammation
mesh term: Stress, Psychological
provided document: 