<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/NCT03756246</url>
  </required_header>
  <id_info>
    <org_study_id>2018030078</org_study_id>
    <nct_id>NCT03756246</nct_id>
  </id_info>
  <brief_title>Influenza Vaccine as a Novel Experimental Model of the Behavioral Immune Response in Depression</brief_title>
  <official_title>Influenza Vaccine as a Novel Experimental Model of the Behavioral Immune Response in Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas at Austin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas at Austin</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>
      The purpose of this study is to determine differences between the immune responses in healthy&#xD;
      and depressed people. Participants will receive the influenza vaccine and their responses&#xD;
      will be monitored. This study will recruit 15 healthy and 60 depressed participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to determine differences between the immune responses in healthy&#xD;
      and depressed people. Specifically subjects are provided a mild immune stimulus, an influenza&#xD;
      vaccine, and their responses are monitored. The goals are to determine whether patients with&#xD;
      depression experience a temporary worsening of mood in response to the stimulus and whether&#xD;
      this is associated with measurable differences in the cytokine response to the vaccine.&#xD;
      Additionally, patients with depression may be less likely to mount a successful antibody&#xD;
      response to vaccination as healthy people based on circumstantial evidence, and this study&#xD;
      will assess whether this the case.&#xD;
&#xD;
      This study aims to recruit a sample of 15 healthy and 60 depressed participants. The 15&#xD;
      healthy participants will be age and gender matched to the first 15 depressed participants&#xD;
      recruited. Three more sets of age and gender matched depressed subjects will be recruited.&#xD;
      This will result in 15 sets of &quot;quintuplets&quot; (4 depressed and one healthy), that are matched&#xD;
      by age and gender. The study consists of four visits. The first visit is the baseline&#xD;
      assessment where participants will receive the influenza vaccine. Participants will then&#xD;
      return 1, 3 and 28 days after receiving the vaccine to assess their responses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 10, 2019</start_date>
  <completion_date type="Anticipated">May 2021</completion_date>
  <primary_completion_date type="Anticipated">May 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Both healthy and depressed arms will receive the influenza vaccine.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Positive and Negative Affect Schedules Score</measure>
    <time_frame>1 Day</time_frame>
    <description>We will compute change in scores on the PANAS-x subscales between baseline and day 1. Self reported assessment that contains both positive and negative words and phrases that describe different feelings and emotions. Subjects read each item and mark the appropriate answer for how they feel right now as they fill out the form. Possible answers and the associated score are: (1) Not at all, (2) A little, (3) Moderately, (4) Quite a bit, (5) Extremely. To rate, responses to items in each scale are summed. The scales in the PANAS are listed below with the number of items in that scale in parentheses followed by the total range of the scale.&#xD;
General Dimensions Negative Affect (10) 10-50 General Dimensions of Positive Affect (10) 10-50 Negative Emotion Fear (6) 6-30 Hostility (6): 6-30 Guilt (6): 6-30 Sadness (5) 5- 25 Positive Emotion Joviality (8) 8-40 Self-Assurance (6) 6-30 Attentiveness (4) 4-20 Other Affective States Shyness (4) 4-20 Fatigue (4) 4-20 Serenity (3) 3-15</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Cytokine Concentration (pg/mL)</measure>
    <time_frame>3 Days</time_frame>
    <description>We will compute differences in cytokine (IFN- α, IFN-y, IL-6, IL1-β and TNF-α) values for each subject between baseline and day 1 and days 1 and 3. Using OLS regression we will compute regressions between hypothesis appropriate time points using baseline CRP, QIDS, PANAS score and BMI as covariates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in PGE4/LipoxinA4 Ratio</measure>
    <time_frame>3 Days</time_frame>
    <description>After determining the difference in the PGE4/LipoxinA4 ratio between days 1 and 3, we will perform a similar regression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tryptophan Metabolites</measure>
    <time_frame>1 Day</time_frame>
    <description>We will calculate difference between baseline and day 1 in the KYN/TRP and KYNA/QUIN ratios and us them in regression models as above, correcting for two tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HPA Axis</measure>
    <time_frame>3 Days</time_frame>
    <description>To test the hypothesis that ACTH/cortisol affects peak inflammatory cytokine levels in MDD, we will use similar OLS regression models including HPA-axis response as a covariate and examining its interaction with cytokines as the dependent variables.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fold Change</measure>
    <time_frame>28 Days</time_frame>
    <description>: Fold change from pre- to 28 days post-vaccine will be calculated for each of the three influenza strains targeted by the vaccine. Fold change &gt; 4 to any one of the three strains will be considered &quot;success.&quot; Proportion of successful vaccination will be compared between HC and MDD using a linear model adjusted for age and pre-vaccination titer, which have been shown to affect antibody response.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Depression</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Depression Subjects: Influenza Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Subjects: Influenza Vaccine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Influenza Vaccine</intervention_name>
    <description>The appropriate quadrivalent influenza vaccine for the give year will be given to subjects.</description>
    <arm_group_label>Depression Subjects: Influenza Vaccine</arm_group_label>
    <arm_group_label>Healthy Subjects: Influenza Vaccine</arm_group_label>
    <other_name>flu shot</other_name>
    <other_name>flu vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria for all subjects&#xD;
&#xD;
          -  Adults age 18-60&#xD;
&#xD;
          -  Able to provide written informed consent directly, without use of a proxy&#xD;
&#xD;
          -  Able to speak and write in English sufficiently to undergo consent and to complete&#xD;
             self reports&#xD;
&#xD;
        Inclusion Criteria for depressed subjects&#xD;
&#xD;
          -  Currently meets criteria for a Depressive Episode and a diagnosis of MDD according&#xD;
             Mini International Neuropsychiatric Interview (MINI)&#xD;
&#xD;
          -  Depressive severity of ≥ 12 on the Quick Inventory of Depression Symptomatology,&#xD;
             Clinician Rated (QIDS-C), corresponding to more than mild depression severity, but&#xD;
             &lt;21, indicating not severe&#xD;
&#xD;
        Inclusion Criteria for healthy Subjects&#xD;
&#xD;
          -  No lifetime Axis I diagnosis on the MINI&#xD;
&#xD;
          -  QIDS-SR score &lt;6 indicating no depression&#xD;
&#xD;
          -  CRP at screening of &lt;1mg/L.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion Criteria for all subjects&#xD;
&#xD;
          -  Active, unstable, or serious medical illness (e.g. requiring urgent out-patient or&#xD;
             higher level of care) as determined by history and lab examination at screening. For&#xD;
             example, subjects with untreated cardiovascular disease (blood pressure above 140/80&#xD;
             on repeated measurements, history of cardiac event without medical follow up) or&#xD;
             untreated diabetes (based on symptoms and elevated fasting blood sugar at screening)&#xD;
             will be excluded.&#xD;
&#xD;
          -  Taking medications that have a significant effect on the immune system. This includes&#xD;
             daily Non-steroidal Anti-inflammatory medications (NSAIDs). As needed NSAIDs will not&#xD;
             be exclusionary but subjects will be asked to refrain from NSAID usage for 48 hours&#xD;
             prior to the vaccination visit and through the day 3 visit.&#xD;
&#xD;
          -  Has received the influenza vaccine for the current season or within the last 12 months&#xD;
&#xD;
          -  Infection with fever or otherwise clinically significant in the last two weeks.&#xD;
             Subjects with elevated white blood cell count at screening will also be excluded.&#xD;
&#xD;
          -  Current and within the last 3 months meeting criteria for tobacco use disorder.&#xD;
&#xD;
          -  Previous severe adverse event associated with IIV&#xD;
&#xD;
          -  History of allergy to any component of the IIV&#xD;
&#xD;
          -  History of Guillain-Barre Syndrome&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Otherwise judged unable to comply with study procedures or unsafe to participate by&#xD;
             study clinician&#xD;
&#xD;
        Exclusion Criteria for Depressed Subjects&#xD;
&#xD;
          -  Life-time history of mania, hypomania, or psychosis on the MINI&#xD;
&#xD;
          -  Meets or has met criteria for substance abuse or dependence in the last 6 months (3&#xD;
             months for nicotine)&#xD;
&#xD;
          -  Meets or has met criteria for any eating disorder in the last 6 months&#xD;
&#xD;
          -  Baseline suicidal ideation above &quot;passive&quot; defined as thoughts of death or dying (e.g.&#xD;
             wish for natural death) without thoughts of active methods (e.g. overdose) or intent&#xD;
             to die, as determined using the Concise Health Risk Tracking Scale (CHRT) (assessment&#xD;
             interval &quot;the last week&quot;) and clinician interview.&#xD;
&#xD;
        No Exclusion Criteria for Healthy Subjects&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Project Coordinator</last_name>
    <phone>512-495-5595</phone>
    <email>behavioral.immunology.lab@dellmed.utexas.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maria Toups, M.D.</last_name>
    <phone>512-494-4672</phone>
    <email>marisa.toups@austin.utexas.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Marisa Toups</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78701</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Project Coordinator</last_name>
      <phone>512-495-5595</phone>
      <email>behavioral.immunology.lab@dellmed.utexas.edu</email>
    </contact>
    <contact_backup>
      <last_name>Alyssa Marron</last_name>
      <phone>512-495-5595</phone>
      <email>alyssa.marron@austin.utexas.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Marisa Toups, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>June 25, 2019</last_update_submitted>
  <last_update_submitted_qc>June 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>depression</keyword>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>depressive</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_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/NCT03756246
org study id: 2018030078
nct id: NCT03756246
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to determine differences between the immune responses in healthy
      and depressed people. Participants will receive the influenza vaccine and their responses
      will be monitored. This study will recruit 15 healthy and 60 depressed participants.
The purpose of this study is to determine differences between the immune responses in healthy
      and depressed people. Specifically subjects are provided a mild immune stimulus, an influenza
      vaccine, and their responses are monitored. The goals are to determine whether patients with
      depression experience a temporary worsening of mood in response to the stimulus and whether
      this is associated with measurable differences in the cytokine response to the vaccine.
      Additionally, patients with depression may be less likely to mount a successful antibody
      response to vaccination as healthy people based on circumstantial evidence, and this study
      will assess whether this the case.

      This study aims to recruit a sample of 15 healthy and 60 depressed participants. The 15
      healthy participants will be age and gender matched to the first 15 depressed participants
      recruited. Three more sets of age and gender matched depressed subjects will be recruited.
      This will result in 15 sets of "quintuplets" (4 depressed and one healthy), that are matched
      by age and gender. The study consists of four visits. The first visit is the baseline
      assessment where participants will receive the influenza vaccine. Participants will then
      return 1, 3 and 28 days after receiving the vaccine to assess their responses.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Both healthy and depressed arms will receive the influenza vaccine.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Positive and Negative Affect Schedules Score
time frame: 1 Day
description: We will compute change in scores on the PANAS-x subscales between baseline and day 1. Self reported assessment that contains both positive and negative words and phrases that describe different feelings and emotions. Subjects read each item and mark the appropriate answer for how they feel right now as they fill out the form. Possible answers and the associated score are: (1) Not at all, (2) A little, (3) Moderately, (4) Quite a bit, (5) Extremely. To rate, responses to items in each scale are summed. The scales in the PANAS are listed below with the number of items in that scale in parentheses followed by the total range of the scale.
General Dimensions Negative Affect (10) 10-50 General Dimensions of Positive Affect (10) 10-50 Negative Emotion Fear (6) 6-30 Hostility (6): 6-30 Guilt (6): 6-30 Sadness (5) 5- 25 Positive Emotion Joviality (8) 8-40 Self-Assurance (6) 6-30 Attentiveness (4) 4-20 Other Affective States Shyness (4) 4-20 Fatigue (4) 4-20 Serenity (3) 3-15
measure: Change in Cytokine Concentration (pg/mL)
time frame: 3 Days
description: We will compute differences in cytokine (IFN- α, IFN-y, IL-6, IL1-β and TNF-α) values for each subject between baseline and day 1 and days 1 and 3. Using OLS regression we will compute regressions between hypothesis appropriate time points using baseline CRP, QIDS, PANAS score and BMI as covariates.
measure: Difference in PGE4/LipoxinA4 Ratio
time frame: 3 Days
description: After determining the difference in the PGE4/LipoxinA4 ratio between days 1 and 3, we will perform a similar regression.
measure: Tryptophan Metabolites
time frame: 1 Day
description: We will calculate difference between baseline and day 1 in the KYN/TRP and KYNA/QUIN ratios and us them in regression models as above, correcting for two tests.
measure: HPA Axis
time frame: 3 Days
description: To test the hypothesis that ACTH/cortisol affects peak inflammatory cytokine levels in MDD, we will use similar OLS regression models including HPA-axis response as a covariate and examining its interaction with cytokines as the dependent variables.
measure: Fold Change
time frame: 28 Days
description: : Fold change from pre- to 28 days post-vaccine will be calculated for each of the three influenza strains targeted by the vaccine. Fold change > 4 to any one of the three strains will be considered "success." Proportion of successful vaccination will be compared between HC and MDD using a linear model adjusted for age and pre-vaccination titer, which have been shown to affect antibody response.
arm group label: Depression Subjects: Influenza Vaccine
arm group type: Experimental
description: Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed
arm group label: Healthy Subjects: Influenza Vaccine
arm group type: Active Comparator
description: Subjects will receive a quadrivalent inactivated influenza vaccine, for the appropriate season/year of enrollment. The vaccine will be administered by the PI or similarly trained clinician, into the deltoid muscle as directed
intervention type: Biological
intervention name: Influenza Vaccine
description: The appropriate quadrivalent influenza vaccine for the give year will be given to subjects.
arm group label: Depression Subjects: Influenza Vaccine
arm group label: Healthy Subjects: Influenza Vaccine
other name: flu shot
other name: flu vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Project Coordinator
phone: 512-495-5595
email: behavioral.immunology.lab@dellmed.utexas.edu
last name: Maria Toups, M.D.
phone: 512-494-4672
email: marisa.toups@austin.utexas.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Vaccines