<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/NCT03294564</url>
  </required_header>
  <id_info>
    <org_study_id>14-13204</org_study_id>
    <secondary_id>K01MH109871</secondary_id>
    <nct_id>NCT03294564</nct_id>
  </id_info>
  <brief_title>Cognitive, Emotional, and Neural Responses to Acute Inflammation</brief_title>
  <official_title>Cognitive, Emotional, and Neural Responses to Acute Inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</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, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a pilot study to examine the effects of acute inflammation on cognition and&#xD;
      emotion in healthy participants using a between-subjects, randomized, double-blind design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The inflammatory response of the immune system is responsive to stress and it impacts brain&#xD;
      function. Animal studies have shown that inflammation appears to alter threat- and&#xD;
      reward-related brain activity. Accumulating evidence points to inflammatory proteins,&#xD;
      specifically cytokines, as key players in this relationship. Although cytokines are typically&#xD;
      too large to pass through the blood brain barrier (BBB), they can influence brain function&#xD;
      and structure by transmitting signals from peripheral systems to the brain.&#xD;
&#xD;
      The administration of endotoxin within the polysaccharide form of Salmonella typhi&#xD;
      vaccination provides an ideal model for studying the causal effects of short-term&#xD;
      inflammation on thinking patterns (i.e., cognition) and emotions in the brain. Endotoxin is a&#xD;
      component of the cell walls of Gram-negative bacteria, which promotes the production of&#xD;
      pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha&#xD;
      (TNF-α) via toll-like receptor-4 (TLR-4) activation and nuclear factor- κB (NF-κB) signaling.&#xD;
&#xD;
      To examine the effects of acute inflammation on brain functioning, 24 healthy participants&#xD;
      will be recruited. The investigators will will randomize participants to placebo or&#xD;
      inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) and will use&#xD;
      validated behavioral tasks and questionnaires to assess threat and reward sensitivity. They&#xD;
      will assess chronic resting levels of inflammation as well as the inflammatory response to&#xD;
      Salmonella typhi vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">December 30, 2018</completion_date>
  <primary_completion_date type="Actual">December 30, 2018</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>Inflammatory markers elicited by the typhoid vaccine</measure>
    <time_frame>5-7 hours</time_frame>
    <description>Participants will receive a vaccine or placebo and investigators will examine inflammation levels during three different time points via blood draws</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Threat sensitivity between groups</measure>
    <time_frame>1-3 hours</time_frame>
    <description>Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reward sensitivity between groups</measure>
    <time_frame>1-2 hours</time_frame>
    <description>Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Typhoid Vi Polysaccharide Vaccine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive one intramuscular 0.5 mL injection of saline placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Typhoid Vi Polysaccharide Vaccine</intervention_name>
    <description>Salmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever.</description>
    <arm_group_label>Typhoid Vi Polysaccharide Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo injection will consist of 0.5mL of saline.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy individuals (free of chronic illness or lifetime history of psychiatric&#xD;
             disorder)&#xD;
&#xD;
          -  Non-smokers&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lifetime history of an psychiatric disorder with psychotic features, bipolar disorder,&#xD;
             obsessive-compulsive disorder, alcohol or substance dependence, or a history of&#xD;
             alcohol or substance abuse within the past 2 years.&#xD;
&#xD;
          -  Currently exposed to recurrent trauma or have been exposed to a traumatic event within&#xD;
             the past 3 months, or has current diagnosis of PTSD.&#xD;
&#xD;
          -  Diagnosis of sleep apnea, neurological disorder, systemic illness affective central&#xD;
             nervous system function, and/or anemia.&#xD;
&#xD;
          -  Any suicidal or homicidal ideation within the past year.&#xD;
&#xD;
          -  Subjects currently receiving selective serotonin reuptake inhibitors (SSRIs),&#xD;
             benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication,&#xD;
             any antidepressant medication including trazodone, or any psychotropic medication.&#xD;
&#xD;
          -  Termination of SSRIs, benzodiazepine or benzodiazepine receptor agonists,&#xD;
             anticonvulsants, atypical antipsychotic medication, any antidepressant medication&#xD;
             including trazodone in the last month, or plans to start these medications during the&#xD;
             course of the study.&#xD;
&#xD;
          -  Contraindications to fMRI, including severe claustrophobia and presence of&#xD;
             ferromagnetic objects in the body that would interfere with magnetic resonance&#xD;
             examination and/or cause a safety risk (e.g., pace makers, implanted stimulators,&#xD;
             pumps, extensive dental work, upper body tattoos).&#xD;
&#xD;
          -  Contraindications to typhoid vaccine, which include acute febrile illness within the&#xD;
             past two weeks, disorders characterized by a deficiency to ability to mount a humoral&#xD;
             or cell-mediated immune response, use of anti-malarial medications in the past six&#xD;
             months, antibiotics in past three months, a history of hypersensitivity to typhoid&#xD;
             vaccine or any other vaccine, pervious immunization with whole-cell typhoid or live,&#xD;
             oral typhoid vaccines, vaccination with the polysaccharide version of the typhoid&#xD;
             vaccine within the past 3 years.&#xD;
&#xD;
          -  Conditions or use of substances that may be associated with inflammation, including&#xD;
             drugs that affect the immune system.&#xD;
&#xD;
          -  Any chronic medical illness.&#xD;
&#xD;
          -  Having a body mass index (BMI) over 30.&#xD;
&#xD;
          -  Individuals who work the night shift&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aoife S O'Donovan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>San Francisco Veterans Affairs Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>June 21, 2019</last_update_submitted>
  <last_update_submitted_qc>June 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Inflammation</keyword>
  <keyword>Threat sensitivity</keyword>
  <keyword>Reward sensitivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03294564
org study id: 14-13204
secondary id: K01MH109871
nct id: NCT03294564
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study is a pilot study to examine the effects of acute inflammation on cognition and
      emotion in healthy participants using a between-subjects, randomized, double-blind design.
The inflammatory response of the immune system is responsive to stress and it impacts brain
      function. Animal studies have shown that inflammation appears to alter threat- and
      reward-related brain activity. Accumulating evidence points to inflammatory proteins,
      specifically cytokines, as key players in this relationship. Although cytokines are typically
      too large to pass through the blood brain barrier (BBB), they can influence brain function
      and structure by transmitting signals from peripheral systems to the brain.

      The administration of endotoxin within the polysaccharide form of Salmonella typhi
      vaccination provides an ideal model for studying the causal effects of short-term
      inflammation on thinking patterns (i.e., cognition) and emotions in the brain. Endotoxin is a
      component of the cell walls of Gram-negative bacteria, which promotes the production of
      pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha
      (TNF-α) via toll-like receptor-4 (TLR-4) activation and nuclear factor- κB (NF-κB) signaling.

      To examine the effects of acute inflammation on brain functioning, 24 healthy participants
      will be recruited. The investigators will will randomize participants to placebo or
      inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) and will use
      validated behavioral tasks and questionnaires to assess threat and reward sensitivity. They
      will assess chronic resting levels of inflammation as well as the inflammatory response to
      Salmonella typhi vaccination.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Inflammatory markers elicited by the typhoid vaccine
time frame: 5-7 hours
description: Participants will receive a vaccine or placebo and investigators will examine inflammation levels during three different time points via blood draws
measure: Threat sensitivity between groups
time frame: 1-3 hours
description: Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity
measure: Reward sensitivity between groups
time frame: 1-2 hours
description: Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity
arm group label: Typhoid Vi Polysaccharide Vaccine
arm group type: Active Comparator
description: Patients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients will receive one intramuscular 0.5 mL injection of saline placebo.
intervention type: Biological
intervention name: Typhoid Vi Polysaccharide Vaccine
description: Salmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever.
arm group label: Typhoid Vi Polysaccharide Vaccine
intervention type: Biological
intervention name: Placebo
description: The placebo injection will consist of 0.5mL of saline.
arm group label: Placebo
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Aoife S O'Donovan, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Inflammation
sharing ipd: Undecided