<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/NCT01671150</url>
  </required_header>
  <id_info>
    <org_study_id>Endotoxin 2</org_study_id>
    <secondary_id>R01MH091352</secondary_id>
    <nct_id>NCT01671150</nct_id>
  </id_info>
  <brief_title>Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms</brief_title>
  <official_title>Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Depressive disorders occur at a high rate in patients with inflammatory disorders, with a&#xD;
      point prevalence of 15-29%, which is two to three times greater than that observed in the&#xD;
      general population. Substantial evidence has shown that inflammation and increases in&#xD;
      proinflammatory cytokine activity play a critical role in the onset and perpetuation of&#xD;
      depression and depressive symptoms (e.g. insomnia, fatigue) in those who are co-morbid for&#xD;
      inflammatory disorders. Consistent with this, experimental work has shown that an&#xD;
      inflammatory challenge can increase depressed mood in an otherwise healthy sample. Based on&#xD;
      these findings, there has been a growing interest in whether inflammatory processes can&#xD;
      contribute to depression in a causal manner and how these effects might occur.&#xD;
&#xD;
      Given the observation that inflammatory processes trigger social withdrawal, coupled with&#xD;
      evidence that feelings of 'social disconnection' play a critical role in the onset and&#xD;
      perpetuation of (non-inflammatory forms of) depression, it is surprising that the social&#xD;
      psychological consequences of inflammation and their contribution to depression have not been&#xD;
      more fully explored. Here, we suggest that inflammation may increase feelings of social&#xD;
      disconnection and that these social psychological changes may be an important contributor to&#xD;
      inflammation-associated depression. Indeed, preliminary data demonstrated that an&#xD;
      experimentally-induced inflammatory challenge (endotoxin) led to increases in self-reported&#xD;
      feelings of social disconnection (e.g., &quot;I feel disconnected from others&quot;) in addition to&#xD;
      increases in depressed mood. Aside from these findings, however, there are no studies that&#xD;
      have explored the effect of inflammatory processes on social experience in humans. The&#xD;
      over-arching objective of this proposal is to explore the experiential and neural correlates&#xD;
      of inflammatory-induced changes in social experience (e.g., feelings of social&#xD;
      disconnection), which may provide a critical missing link in understanding the relationship&#xD;
      between inflammation and depression.&#xD;
&#xD;
      Participants (n=100) will be randomly assigned to receive either endotoxin or placebo and&#xD;
      will then be monitored for the next six hours. Blood draws to assess cytokine levels as well&#xD;
      as self-reported feelings of social disconnection and depressed mood will be collected&#xD;
      hourly. In addition, at the time of peak cytokine response, participants will complete a&#xD;
      neuroimaging session to examine the effect of inflammatory challenge on neural sensitivity to&#xD;
      social rejection and social acceptance. It is hypothesized that endotoxin will increase&#xD;
      feelings of social disconnection over time, and that the underlying neural sensitivities that&#xD;
      give rise to these feelings (e.g., increased neural sensitivity to social rejection;&#xD;
      decreased neural sensitivity to social acceptance) will contribute to inflammatory-induced&#xD;
      depressed mood.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2011</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <phase>Early Phase 1</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in depressed mood from baseline</measure>
    <time_frame>at baseline and then at 1,2,3,4,5,and 6 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neural activity to negative and positive social feedback</measure>
    <time_frame>2 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Placebo control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>half of the participants will receive a placebo control</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Endotoxin (Inflammatory challenge)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>endotoxin</intervention_name>
    <description>Low-dose endotoxin (0.8 ng/kg of body weight): EC.O:113 administered once</description>
    <arm_group_label>Endotoxin (Inflammatory challenge)</arm_group_label>
    <arm_group_label>Placebo control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants will be required to be in good general health (as evaluated during the&#xD;
             phone and in-person screening sessions described below), and to be between 18-50 years&#xD;
             of age. All participants will be required to be fluent in English and to be&#xD;
             right-handed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Following a structured telephone interview, prospective participants with the&#xD;
             following conditions will not advance to the in-person screening session:&#xD;
             claustrophobia or presence of metal in their body (relevant for the neuroimaging&#xD;
             component of the study), pregnant or planning to become pregnant in the next 6 months,&#xD;
             presence of chronic mental or physical illness, history of allergies, autoimmune,&#xD;
             liver, or other severe chronic diseases, current and regular use of prescription&#xD;
             medications, nightshift work or time zone shifts (&gt; 3hrs) within the previous 6 weeks,&#xD;
             or previous history of fainting during blood draws.&#xD;
&#xD;
        Furthermore, the absence of significant health problems or medication use history will be&#xD;
        confirmed by an in-person screening session. Any participant who has any of the following&#xD;
        conditions will be ineligible for the study: Medical conditions. (1) presence of co-morbid&#xD;
        medical conditions not limited to but including cardiovascular (e.g., history of acute&#xD;
        coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as&#xD;
        pain disorders; (2) presence of co-morbid inflammatory disorders such as rheumatoid&#xD;
        arthritis or other autoimmune disorders; (3) presence of an uncontrolled medical condition&#xD;
        that is deemed by the investigators to interfere with the proposed study procedures, or to&#xD;
        put the study participant at undue risk; (4) presence of chronic infection, which may&#xD;
        elevate proinflammatory cytokines; (5) presence of an acute infectious illness in the two&#xD;
        weeks prior to an experimental session. Psychiatric Disorders. (6) current and/or lifetime&#xD;
        history of a major Depressive Disorder or other DSM-IV psychiatric disorder (e.g. substance&#xD;
        dependence) due to the known effects of major depression and/or substance dependence on&#xD;
        inflammation. (Absence of a psychiatric diagnosis will be based on a structured psychiatric&#xD;
        interview (Structured Clinical Interview for DSM-IV Diagnosis: SCID; First et al., 1996).)&#xD;
        Medication and substance use. (7) current and/or past regular use of hormone-containing&#xD;
        medications including steroids; (8) current and/or past regular use of non-steroid&#xD;
        anti-inflammatory drugs; (9) current and/or past regular use of immune modifying drugs that&#xD;
        target specific immune responses such as TNF antagonists; (10) current and/or past regular&#xD;
        use of analgesics such as opioids; (11) current and/or past regular use of psychotropic&#xD;
        medications, including selective serotinergic reuptake inhibitors, antidepressants,&#xD;
        anxiolytics, hypnotics, sedatives and barbiturates. Health factors. (12) current smokers or&#xD;
        excessive caffeine users (&gt;600 mg/day) because of known effects on proinflammatory cytokine&#xD;
        levels; (13) body mass index (BMI) greater than 35, (14) shows evidence of drug use from a&#xD;
        positive urine test, (15) has a positive pregnancy test, if female, or (16) shows any&#xD;
        abnormalities on screening laboratory tests.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Naomi Eisenberger, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Irwin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA Clinical &amp; Translational Research Center</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>June 2014</verification_date>
  <study_first_submitted>July 11, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <last_update_submitted>June 16, 2014</last_update_submitted>
  <last_update_submitted_qc>June 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 18, 2014</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>Naomi Eisenberger</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>inflammation</keyword>
  <keyword>depression</keyword>
  <keyword>social cognition</keyword>
  <keyword>neural activity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Depression</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/NCT01671150
org study id: Endotoxin 2
secondary id: R01MH091352
nct id: NCT01671150
lead sponsor: 
collaborator: 
has dmc: Yes
Depressive disorders occur at a high rate in patients with inflammatory disorders, with a
      point prevalence of 15-29%, which is two to three times greater than that observed in the
      general population. Substantial evidence has shown that inflammation and increases in
      proinflammatory cytokine activity play a critical role in the onset and perpetuation of
      depression and depressive symptoms (e.g. insomnia, fatigue) in those who are co-morbid for
      inflammatory disorders. Consistent with this, experimental work has shown that an
      inflammatory challenge can increase depressed mood in an otherwise healthy sample. Based on
      these findings, there has been a growing interest in whether inflammatory processes can
      contribute to depression in a causal manner and how these effects might occur.

      Given the observation that inflammatory processes trigger social withdrawal, coupled with
      evidence that feelings of 'social disconnection' play a critical role in the onset and
      perpetuation of (non-inflammatory forms of) depression, it is surprising that the social
      psychological consequences of inflammation and their contribution to depression have not been
      more fully explored. Here, we suggest that inflammation may increase feelings of social
      disconnection and that these social psychological changes may be an important contributor to
      inflammation-associated depression. Indeed, preliminary data demonstrated that an
      experimentally-induced inflammatory challenge (endotoxin) led to increases in self-reported
      feelings of social disconnection (e.g., "I feel disconnected from others") in addition to
      increases in depressed mood. Aside from these findings, however, there are no studies that
      have explored the effect of inflammatory processes on social experience in humans. The
      over-arching objective of this proposal is to explore the experiential and neural correlates
      of inflammatory-induced changes in social experience (e.g., feelings of social
      disconnection), which may provide a critical missing link in understanding the relationship
      between inflammation and depression.

      Participants (n=100) will be randomly assigned to receive either endotoxin or placebo and
      will then be monitored for the next six hours. Blood draws to assess cytokine levels as well
      as self-reported feelings of social disconnection and depressed mood will be collected
      hourly. In addition, at the time of peak cytokine response, participants will complete a
      neuroimaging session to examine the effect of inflammatory challenge on neural sensitivity to
      social rejection and social acceptance. It is hypothesized that endotoxin will increase
      feelings of social disconnection over time, and that the underlying neural sensitivities that
      give rise to these feelings (e.g., increased neural sensitivity to social rejection;
      decreased neural sensitivity to social acceptance) will contribute to inflammatory-induced
      depressed mood.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Change in depressed mood from baseline
time frame: at baseline and then at 1,2,3,4,5,and 6 hours after drug administration
measure: Neural activity to negative and positive social feedback
time frame: 2 hours after drug administration
arm group label: Placebo control
arm group type: Placebo Comparator
description: half of the participants will receive a placebo control
arm group label: Endotoxin (Inflammatory challenge)
arm group type: Active Comparator
intervention type: Drug
intervention name: endotoxin
description: Low-dose endotoxin (0.8 ng/kg of body weight): EC.O:113 administered once
arm group label: Endotoxin (Inflammatory challenge)
arm group label: Placebo control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Naomi Eisenberger, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Michael Irwin, M.D.
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: Naomi Eisenberger
investigator title: Assistant Professor
mesh term: Inflammation
mesh term: Depression