<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/NCT01710202</url>
  </required_header>
  <id_info>
    <org_study_id>2011-12-0017</org_study_id>
    <nct_id>NCT01710202</nct_id>
  </id_info>
  <brief_title>Sensitivity of Short and Long Allele Carriers of the 5-HTTLPR to Environmental Threat Post Hydrocortisone Administration</brief_title>
  <acronym>5-HTTLPR</acronym>
  <official_title>Sensitivity of Short and Long Allele Carriers of the 5-HTTLPR to Environmental Threat Post Hydrocortisone Administration</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current study will test the causal relationship between elevated levels of cortisol and&#xD;
      the serotonin transporter gene (5-HTTLPR) as these factors influence sensitivity to&#xD;
      environmental threat. The investigators predict that carriers of the short allele of the&#xD;
      serotonin transporter gene who have elevated cortisol levels will be most sensitive to&#xD;
      threatening environments, whereas carriers of the long allele who do not have elevated&#xD;
      cortisol (placebo subjects) will be least sensitive.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Depression vulnerability has been linked to certain variants of the serotonin transporter&#xD;
      gene. Research indicates that a polymorphism of the serotonin transporter (5-HTTLPR) gene&#xD;
      appears to moderate the association between life stress and depression onset. Life stress&#xD;
      robustly predicts depression onset for individuals with two short 5-HTTLPR alleles.&#xD;
      Individuals homozygous for the short 5-HTTLPR allele thus appear to be more sensitive to the&#xD;
      effect of life stress, which in turn contributes to depression onset. A recent study showed&#xD;
      that short allele carriers presented with a threat (social or other threats) who also had&#xD;
      high levels of testosterone had elevated cortisol after exposure to the threat. There is&#xD;
      neurobiological evidence that short allele status, elevated testosterone levels, and elevated&#xD;
      cortisol levels are all linked to amygdala hyper-reactivity to the same classes of&#xD;
      environmental threats. Thus, this study will test, for the first time, a potential&#xD;
      interaction between 5-HTTLPR status and experimentally manipulated cortisol levels as risk&#xD;
      factors for downstream mood and/or anxiety disorders by examining potential dysregulated&#xD;
      stress responses among short allele carriers who have elevated cortisol levels.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
  </study_design_info>
  <primary_outcome>
    <measure>Change in testosterone concentration</measure>
    <time_frame>2 hours post hydrocortisone administration</time_frame>
    <description>Subjects will be administered hydrocortisone or placebo. One hour after administration, they will be exposed to an environmental threat manipulation. 20 minutes after this manipulation, saliva will be collected, and testosterone concentrations will be assessed and compared to pre-manipulation concentrations</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">120</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Anxiety Disorders</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <description>Control group who will not receive hydrocortisone. Will act as a comparison group to the hydrocortisone group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Hydrocortisone</arm_group_label>
    <description>Group will receive 20mg oral hydrocortisone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocortisone</intervention_name>
    <description>Each subject in this group will receive one 20mg hydrocortisone capsule to be taken by mouth.</description>
    <arm_group_label>Experimental: Hydrocortisone</arm_group_label>
    <other_name>Cortef</other_name>
    <other_name>Cortisol</other_name>
    <other_name>Hydrocortone</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Saliva&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        University of Texas at Austin students&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  None&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are you under the age of 18 years old?&#xD;
&#xD;
          -  Have you ever had an allergic reaction to hydrocortisone?&#xD;
&#xD;
          -  Do you have diabetes or high blood pressure?&#xD;
&#xD;
          -  Do you have any thyroid, liver, heart, lung, or kidney problems?&#xD;
&#xD;
          -  Do you have herpes, HIV or any sexual transmitted disease?&#xD;
&#xD;
          -  Are you currently pregnant or think you might be pregnant? Have you taken RU486, Plan&#xD;
             B or &quot;Morning After Pill&quot; within the last 2 weeks? - Are you currently breastfeeding?&#xD;
&#xD;
          -  Have you been sick within the last week? Do you have any fungal infections?&#xD;
&#xD;
          -  Have you been exposed to measles or chicken pox in the last week?&#xD;
&#xD;
          -  Have you ever had a seizure?&#xD;
&#xD;
          -  Do you have any disease of bony tissue, such as osteoporosis?&#xD;
&#xD;
          -  Do you have any autoimmune diseases, such as myasthenia gravis?&#xD;
&#xD;
          -  Do you have multiple sclerosis?&#xD;
&#xD;
          -  Do you have any condition that compromises you immune system function or causes you to&#xD;
             be more likely to get sick?&#xD;
&#xD;
          -  Have you had any recent surgeries?&#xD;
&#xD;
          -  Do you have and gastrointestinal problems, such as ulcers, diverticulitis, colitis,&#xD;
             hepatitis, or Crohn disease?&#xD;
&#xD;
          -  Are you taking any of the following medications: nevirapine, telbivudine, sipuleucel-T&#xD;
             (IV), natalizumab (IV)?&#xD;
&#xD;
          -  Have you received any vaccinations within the last week?&#xD;
&#xD;
          -  With the exception of vitamins, have you taken any medications in the last 3 days,&#xD;
             including all over-the counter medications and/or supplements (e,g. Tylenol,&#xD;
             ibuprofen, St. John's Wort, cold remedies)?&#xD;
&#xD;
          -  Do you currently have or have you had in the past of any kind of cancer?&#xD;
&#xD;
          -  Do you have any significant medical or psychiatric illnesses not listed above?&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert A Josephs, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas at Austin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas at Austin Department of Psychology</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas at Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Josephs RA, Telch MJ, Hixon JG, Evans JJ, Lee H, Knopik VS, McGeary JE, Hariri AR, Beevers CG. Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype x testosterone interaction. Psychoneuroendocrinology. 2012 Jun;37(6):752-61. doi: 10.1016/j.psyneuen.2011.09.006. Epub 2011 Oct 5.</citation>
    <PMID>21978869</PMID>
  </reference>
  <verification_date>August 2013</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 19, 2012</study_first_posted>
  <last_update_submitted>March 18, 2015</last_update_submitted>
  <last_update_submitted_qc>March 18, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 20, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hydrocortisone</keyword>
  <keyword>Cortisol</keyword>
  <keyword>Testosterone</keyword>
  <keyword>Stress</keyword>
  <keyword>Serotonin</keyword>
  <keyword>5-HTTLPR</keyword>
  <keyword>Amygdala</keyword>
  <keyword>Depression</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>
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrocortisone</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/NCT01710202
org study id: 2011-12-0017
nct id: NCT01710202
lead sponsor: 
has dmc: Yes
The current study will test the causal relationship between elevated levels of cortisol and
      the serotonin transporter gene (5-HTTLPR) as these factors influence sensitivity to
      environmental threat. The investigators predict that carriers of the short allele of the
      serotonin transporter gene who have elevated cortisol levels will be most sensitive to
      threatening environments, whereas carriers of the long allele who do not have elevated
      cortisol (placebo subjects) will be least sensitive.
Depression vulnerability has been linked to certain variants of the serotonin transporter
      gene. Research indicates that a polymorphism of the serotonin transporter (5-HTTLPR) gene
      appears to moderate the association between life stress and depression onset. Life stress
      robustly predicts depression onset for individuals with two short 5-HTTLPR alleles.
      Individuals homozygous for the short 5-HTTLPR allele thus appear to be more sensitive to the
      effect of life stress, which in turn contributes to depression onset. A recent study showed
      that short allele carriers presented with a threat (social or other threats) who also had
      high levels of testosterone had elevated cortisol after exposure to the threat. There is
      neurobiological evidence that short allele status, elevated testosterone levels, and elevated
      cortisol levels are all linked to amygdala hyper-reactivity to the same classes of
      environmental threats. Thus, this study will test, for the first time, a potential
      interaction between 5-HTTLPR status and experimentally manipulated cortisol levels as risk
      factors for downstream mood and/or anxiety disorders by examining potential dysregulated
      stress responses among short allele carriers who have elevated cortisol levels.
observational model: Case-Control
measure: Change in testosterone concentration
time frame: 2 hours post hydrocortisone administration
description: Subjects will be administered hydrocortisone or placebo. One hour after administration, they will be exposed to an environmental threat manipulation. 20 minutes after this manipulation, saliva will be collected, and testosterone concentrations will be assessed and compared to pre-manipulation concentrations
arm group label: Placebo
description: Control group who will not receive hydrocortisone. Will act as a comparison group to the hydrocortisone group.
arm group label: Experimental: Hydrocortisone
description: Group will receive 20mg oral hydrocortisone
intervention type: Drug
intervention name: Hydrocortisone
description: Each subject in this group will receive one 20mg hydrocortisone capsule to be taken by mouth.
arm group label: Experimental: Hydrocortisone
other name: Cortef
other name: Cortisol
other name: Hydrocortone
Saliva
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Robert A Josephs, Ph.D.
role: Principal Investigator
affiliation: University of Texas at Austin
facility: 
facility: 
country: United States
citation: Josephs RA, Telch MJ, Hixon JG, Evans JJ, Lee H, Knopik VS, McGeary JE, Hariri AR, Beevers CG. Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype x testosterone interaction. Psychoneuroendocrinology. 2012 Jun;37(6):752-61. doi: 10.1016/j.psyneuen.2011.09.006. Epub 2011 Oct 5.
PMID: 21978869
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Anxiety Disorders
mesh term: Hydrocortisone