<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/NCT02193204</url>
  </required_header>
  <id_info>
    <org_study_id>1111009349</org_study_id>
    <secondary_id>1R01AA02009501A</secondary_id>
    <nct_id>NCT02193204</nct_id>
  </id_info>
  <brief_title>Chronic Alcohol, Stress Inflammatory Response and Relapse Risk</brief_title>
  <official_title>Chronic Alcohol, Stress Inflammatory Response and Relapse Risk</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine potential stress and immune systems adaptations&#xD;
      underlying craving and relapse vulnerability in alcohol dependent (AD) individuals and social&#xD;
      drinkers (SDs) with and without high levels of depressive symptomatology (+dep / - dep).&#xD;
      Using the investigators experimentally validated guided imagery procedure, the investigators&#xD;
      propose to examine the response of brain stress and immune systems to personalized guided&#xD;
      stressful imagery using subjective, physiological and neurobiological assessments in 60&#xD;
      healthy controls and 60 alcoholic dependent individuals with and without depressive&#xD;
      symptomatology.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2011</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>cytokine levels</measure>
    <time_frame>Day 1 and 2, (-25, -5, +5, +15, +30, +45)</time_frame>
    <description>At each of the six time-points (-25, -5, +5, +15, +30, +45), serum cytokine concentrations of IL-6, TNFa, TNFR1, IL-10, IL1-ra, IL-4, IL1beta, and IL-12 will be collected. Levels will be determined by enzyme-linked immuno-sorbent assays using the DuoSet ELISA Development Kit from R&amp;D systems (Minneapolis, MN, USA). Plasma Cortisol and ACTH levels will also be colected and assays will be measured using standard radioimmunoassay procedures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Alcohol Craving</measure>
    <time_frame>Day 14, Day 30 and Day 90</time_frame>
    <description>Participants will rate their desire to have an alcoholic drink as well as how anxious they feel at that moment using a10-point visual analog scale (VAS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety and Negative Mood</measure>
    <time_frame>Day 14, Day 30 and Day 90</time_frame>
    <description>Differential Emotion Scale - DES (Izard, 1972): Subjects are required to rate on a 5-point scale the extent to which an emotional word (item) describes the way s/he feels at the current time. Data is collapsed into subscales: anger, anxiety, fear, sadness, joy, and relaxed state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol Relapse</measure>
    <time_frame>14, 30 and 90 day follow-ups</time_frame>
    <description>Relapse will be defined as a dichotomous variable and any alcohol use during the ninety days post discharge will be coded as relapse.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Alcohol Dependence</condition>
  <condition>Depressive Symptomatology</condition>
  <arm_group>
    <arm_group_label>Social Drinkers Depressive Symptoms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 non-dependent light socially drinking (SD) smokers with depressive symptoms will be recruited to participate in two laboratory sessions (Stress and Neutral / Relaxing). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Social Drinkers No Depressive Symptoms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 non-dependent light socially drinking (SD) smokers without depressive symptoms will be recruited to participate in two laboratory sessions (Stress and Neutral / Relaxing). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alcohol Dependent, Non-Depressive</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 treatment-engaged 28-day abstinent, alcohol dependent (AD) smokers, without Depressive symptoms. All AD subjects will either be admitted to the Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center for five weeks of inpatient stay and study participation (inpatient), or they will be scheduled for a two night stay on the CNRU following 3 weeks of abstinence (outpatient). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alchohol Dependent Depressive Symptoms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 treatment-engaged 28-day abstinent, alcohol dependent smokers with depressive symptoms. All AD subjects will either be admitted to the Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center for five weeks of inpatient stay and study participation (inpatient), or they will be scheduled for a two night stay on the CNRU following 3 weeks of abstinence (outpatient). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Personal Stress Imagery</intervention_name>
    <description>The stress imagery script will be based on participants' description of a recent personal event experienced as &quot;most stressful&quot;, and determined as such by rating it above 8 on a 10-point stress scale. These may include breakup with a significant other or job-related stress. A 5-minute 'script' of each scenario will be written using Scene Construction Questionnaires where physiological, bodily sensations regarding the event will be obtained. Scripts will then be recorded onto audiotape for guided imagery in the laboratory sessions.</description>
    <arm_group_label>Alchohol Dependent Depressive Symptoms</arm_group_label>
    <arm_group_label>Alcohol Dependent, Non-Depressive</arm_group_label>
    <arm_group_label>Social Drinkers Depressive Symptoms</arm_group_label>
    <arm_group_label>Social Drinkers No Depressive Symptoms</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Neutral Imagery</intervention_name>
    <description>The neutral script will be developed from a personal non-alcohol-related relaxing situation. A 5-minute 'script' of each scenario will be written using Scene Construction Questionnaires where physiological, bodily sensations regarding the event will be obtained. Scripts will then be recorded onto audiotape for guided imagery in the laboratory sessions.</description>
    <arm_group_label>Alchohol Dependent Depressive Symptoms</arm_group_label>
    <arm_group_label>Alcohol Dependent, Non-Depressive</arm_group_label>
    <arm_group_label>Social Drinkers Depressive Symptoms</arm_group_label>
    <arm_group_label>Social Drinkers No Depressive Symptoms</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ADs: Male and females, aged 18-50 years, meeting current DSM-IV criteria for alcohol&#xD;
             dependence consuming more than 25 drinks / week.&#xD;
&#xD;
          -  SDs: Male and females, aged 18-50 years. Must not meet either current or lifetime&#xD;
             DSM-IV criteria for alcohol/drug abuse. They must have demonstrated weekly alcohol use&#xD;
             over the past year but no more than 25 drinks / month with no occasion of binge&#xD;
             drinking (5 or more drinks-men; 4 or more -women).&#xD;
&#xD;
          -  ADs and SDs must self-report depression ratings at levels to match one of the two&#xD;
             following groups: a) a score of 20 or above in the Center for Epidemiologic Studies -&#xD;
             Depression Scale (CES-D), or b) a score between 3 -20 on the CES-D&#xD;
&#xD;
          -  Weekly alcohol use as documented by positive urine toxicology screens (AD only).&#xD;
&#xD;
          -  Good health as verified by screening examinations and medical and screening&#xD;
&#xD;
          -  Able to read English and complete study evaluations.&#xD;
&#xD;
          -  All participants must voluntarily provide informed consent and sign the informed&#xD;
             consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Meeting current criteria for dependence on another psychoactive substance, excluding&#xD;
             nicotine.&#xD;
&#xD;
          -  Having any current Axis I psychiatric disorders and requiring treatment/medication for&#xD;
             these conditions.&#xD;
&#xD;
          -  Having significant underlying medical conditions requiring medication.&#xD;
&#xD;
          -  Women who are pregnant or nursing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Helen Fox, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CT Mental Health Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>March 4, 2020</last_update_submitted>
  <last_update_submitted_qc>March 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alcohol dependence</keyword>
  <keyword>Stress</keyword>
  <keyword>Cytokines</keyword>
  <keyword>Depressive Symptomatology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</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/NCT02193204
org study id: 1111009349
secondary id: 1R01AA02009501A
nct id: NCT02193204
lead sponsor: 
has dmc: No
The purpose of this study is to examine potential stress and immune systems adaptations
      underlying craving and relapse vulnerability in alcohol dependent (AD) individuals and social
      drinkers (SDs) with and without high levels of depressive symptomatology (+dep / - dep).
      Using the investigators experimentally validated guided imagery procedure, the investigators
      propose to examine the response of brain stress and immune systems to personalized guided
      stressful imagery using subjective, physiological and neurobiological assessments in 60
      healthy controls and 60 alcoholic dependent individuals with and without depressive
      symptomatology.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: cytokine levels
time frame: Day 1 and 2, (-25, -5, +5, +15, +30, +45)
description: At each of the six time-points (-25, -5, +5, +15, +30, +45), serum cytokine concentrations of IL-6, TNFa, TNFR1, IL-10, IL1-ra, IL-4, IL1beta, and IL-12 will be collected. Levels will be determined by enzyme-linked immuno-sorbent assays using the DuoSet ELISA Development Kit from R&D systems (Minneapolis, MN, USA). Plasma Cortisol and ACTH levels will also be colected and assays will be measured using standard radioimmunoassay procedures.
measure: Alcohol Craving
time frame: Day 14, Day 30 and Day 90
description: Participants will rate their desire to have an alcoholic drink as well as how anxious they feel at that moment using a10-point visual analog scale (VAS).
measure: Anxiety and Negative Mood
time frame: Day 14, Day 30 and Day 90
description: Differential Emotion Scale - DES (Izard, 1972): Subjects are required to rate on a 5-point scale the extent to which an emotional word (item) describes the way s/he feels at the current time. Data is collapsed into subscales: anger, anxiety, fear, sadness, joy, and relaxed state.
measure: Alcohol Relapse
time frame: 14, 30 and 90 day follow-ups
description: Relapse will be defined as a dichotomous variable and any alcohol use during the ninety days post discharge will be coded as relapse.
arm group label: Social Drinkers Depressive Symptoms
arm group type: Experimental
description: 30 non-dependent light socially drinking (SD) smokers with depressive symptoms will be recruited to participate in two laboratory sessions (Stress and Neutral / Relaxing). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.
arm group label: Social Drinkers No Depressive Symptoms
arm group type: Experimental
description: 30 non-dependent light socially drinking (SD) smokers without depressive symptoms will be recruited to participate in two laboratory sessions (Stress and Neutral / Relaxing). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.
arm group label: Alcohol Dependent, Non-Depressive
arm group type: Experimental
description: 30 treatment-engaged 28-day abstinent, alcohol dependent (AD) smokers, without Depressive symptoms. All AD subjects will either be admitted to the Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center for five weeks of inpatient stay and study participation (inpatient), or they will be scheduled for a two night stay on the CNRU following 3 weeks of abstinence (outpatient). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.
arm group label: Alchohol Dependent Depressive Symptoms
arm group type: Experimental
description: 30 treatment-engaged 28-day abstinent, alcohol dependent smokers with depressive symptoms. All AD subjects will either be admitted to the Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center for five weeks of inpatient stay and study participation (inpatient), or they will be scheduled for a two night stay on the CNRU following 3 weeks of abstinence (outpatient). This arm will be exposed to both the personal stress imagery and neutral imagery interventions.
intervention type: Behavioral
intervention name: Personal Stress Imagery
description: The stress imagery script will be based on participants' description of a recent personal event experienced as "most stressful", and determined as such by rating it above 8 on a 10-point stress scale. These may include breakup with a significant other or job-related stress. A 5-minute 'script' of each scenario will be written using Scene Construction Questionnaires where physiological, bodily sensations regarding the event will be obtained. Scripts will then be recorded onto audiotape for guided imagery in the laboratory sessions.
arm group label: Alchohol Dependent Depressive Symptoms
arm group label: Alcohol Dependent, Non-Depressive
arm group label: Social Drinkers Depressive Symptoms
arm group label: Social Drinkers No Depressive Symptoms
intervention type: Behavioral
intervention name: Neutral Imagery
description: The neutral script will be developed from a personal non-alcohol-related relaxing situation. A 5-minute 'script' of each scenario will be written using Scene Construction Questionnaires where physiological, bodily sensations regarding the event will be obtained. Scripts will then be recorded onto audiotape for guided imagery in the laboratory sessions.
arm group label: Alchohol Dependent Depressive Symptoms
arm group label: Alcohol Dependent, Non-Depressive
arm group label: Social Drinkers Depressive Symptoms
arm group label: Social Drinkers No Depressive Symptoms
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Helen Fox, PhD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism