<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/NCT04412824</url>
  </required_header>
  <id_info>
    <org_study_id>19-263 MR 1907</org_study_id>
    <secondary_id>R00AA025401</secondary_id>
    <nct_id>NCT04412824</nct_id>
  </id_info>
  <brief_title>Multimodal Neuroimaging of Alcohol Cues, Cortisol Response, and Compulsive Motivation</brief_title>
  <official_title>Multimodal Neuroimaging of Alcohol Cues, Cortisol Response, and Compulsive Motivation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Auburn University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Auburn University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study proposes to examine both the peripheral and central nervous system responses when&#xD;
      light social drinkers and binge/heavy social drinkers are exposed to visual ethanol cues,&#xD;
      followed by oral ethanol. The findings will provide a greater understanding of the brain&#xD;
      mechanisms (cerebral blood flow and functional connectivity) underlying the association&#xD;
      between stress, cortisol release, alcohol craving, and alcohol stimulant and sedative&#xD;
      effects. This knowledge could be significant in developing new therapies for the treatment of&#xD;
      alcoholism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Results from the 2014 National Survey on Drug Use and Health show that 26% of adults in the&#xD;
      US engaged in binge drinking in the past month (SAMHSA 2014). Why some people &quot;mature out&quot; of&#xD;
      this behavior while others persist may be due to one's physiological response to binge&#xD;
      drinking. No previous study has assessed whether disrupted cortisol and neural network&#xD;
      responses to alcohol cues may drive the compulsive alcohol consumption seen in binge drinking&#xD;
      individuals who do not yet have an AUD.&#xD;
&#xD;
      The investigator will recruit beer drinking, non-smoking men and women ages 21-45 (N=80,&#xD;
      equal gender) who are either moderate drinkers or binge/heavy drinkers for two neuroimaging&#xD;
      and neuroendocrine assessments to determine if their &quot;real world&quot; drinking behavior, in a&#xD;
      prospective one month follow up, can be predicted based upon the cortisol and neural network&#xD;
      responses to alcohol cues (with a placebo control, counter-balanced and randomized). Finally,&#xD;
      the influence of genetic variation in the FK506-binding protein 5 (FKBP5) gene, which&#xD;
      regulates cortisol activity, on the cortisol and neural network responses to alcohol cues&#xD;
      will be explored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Neural Blood Flow</measure>
    <time_frame>During the Procedure: measurements taken at 10, 20, 30 and 45 minutes during the procedure.</time_frame>
    <description>Blood flow is measured in ml/100 grams/minute. The interpretation is that blood flow to that area indicates that region of the brain is responding to the visual alcohol or non-alcoholic beverage cues. Change in blood flow will be calculated as the change (and slope) of measurements taken at 10, 20, 30 and 45 minutes during the procedure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Cortisol</measure>
    <time_frame>Before Procedure to 125 minutes after the procedure.</time_frame>
    <description>The units for cortisol are micrograms/deciliter and the interpretation is that amount has been released into the blood stream from the HPA axis in response to alcohol or alcohol cues. Change in Cortisol will be calculated by taking the change (and slopes) of measurements at 45, 30 and 5 minutes prior to procedure and comparing it to measurements taken at 65, 95, 110, 125 minutes following the procedure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Drinking Behavior in daily experience outside of laboratory</measure>
    <time_frame>Day after Procedure to 30 days after procedure.</time_frame>
    <description>A smartphone app will be used to collect 4 surveys a day for 30 days after completion of both arms. Multilevel modeling will be used to analyze patterns of drinking over time.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Amount of Alcohol Consumed</measure>
    <time_frame>Immediately after the procedure.</time_frame>
    <description>After exposure to alcoholic beverage and non-alcoholic beverage visual cues, quantity of alcohol consumed in a free choice test will be measured in milliliters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Alcohol Urges (AUQ)</measure>
    <time_frame>Before Procedure to 125 minutes after the procedure.</time_frame>
    <description>The urge to consume alcohol will be measured using the Alcohol Urge Questionnaire (AUQ). The AUQ consists of 8 questions 8-56 total point distribution. The greater the total points, the greater the measured urge to consume alcohol. The change in alcohol urge will be assessed with the taking the change (and slopes) of measurements at 45, 30 and 5 minutes prior to procedure and comparing it to measurements taken at 65, 95, 110, 125 minutes following the procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stress levels in daily experience outside of laboratory</measure>
    <time_frame>Post follow-up procedure (30 days)</time_frame>
    <description>A smartphone app will be used to collect 4 surveys a day for 30 days after completion of both arms. Multilevel modeling will be used to analyze subjective experience of stress over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic Risk Factors (Single Nucleotide Polymorphisms; SNPs) Association with Cerebral Blood Flow, Craving, and Real world drinking and stress</measure>
    <time_frame>Post follow up procedure (within 2 years after procedure)</time_frame>
    <description>One sample of whole blood will be obtained and analyzed for genomic associations with other outcome measures.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Alcohol Beverage Cues</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will complete an MRI with alcohol beverage visual cues and oral alcohol session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Alcoholic Beverage Cues</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will complete an MRI with non-alcoholic beverage cues and oral alcohol session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous blood draw</intervention_name>
    <description>In addition to the oral delivery, an IV line will be placed for the purpose of drawing blood during the MRI session</description>
    <arm_group_label>Alcohol Beverage Cues</arm_group_label>
    <arm_group_label>Non-Alcoholic Beverage Cues</arm_group_label>
    <other_name>Indwelling catheter for blood draws</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Binge/Heavy Social Drinkers (HSD): has never met DSM-IV criteria for alcohol or&#xD;
             substance dependence; regular alcohol use over the past year of at least 10 drinks per&#xD;
             week, including at lease one occasion per week consuming &gt;4 drinks (males) or &gt;3&#xD;
             drinks (females).&#xD;
&#xD;
          -  Able to read and write English.&#xD;
&#xD;
          -  Light Social Drinkers (LSD): has never met DSM-IV criteria for alcohol or substance&#xD;
             dependence; regular alcohol use over the past year of 1-3 drinks per occasion, 1-3&#xD;
             times weekly, with no more than one occasion per month of drinking &gt;4 drinks (male) or&#xD;
             &gt;3 drinks (females) (King et al., 2002).&#xD;
&#xD;
          -  Do not meet criteria for any Axis I DSM-IV psychiatric diagnoses except for&#xD;
             individuals with a past diagnosis of Post-Traumatic Stress Disorder, Major Depressive&#xD;
             Disorder, or Obsessive Compulsive Disorder&#xD;
&#xD;
          -  Provide negative urine toxicology screens during initial appointments and at admission&#xD;
             for IV/fMRI sessions.&#xD;
&#xD;
          -  Body Mass Index between 20-35.&#xD;
&#xD;
          -  No current or former nicotine dependence.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Meet current criteria for dependence on any psychoactive substance, excluding&#xD;
             caffeine.&#xD;
&#xD;
          -  Current or past history of alcohol dependence or abuse.&#xD;
&#xD;
          -  Any current use of opiates or past history of opiate abuse/dependence.&#xD;
&#xD;
          -  Current use of any psychoactive drugs, including anxiolytics, antidepressants,&#xD;
             naltrexone or antabuse.&#xD;
&#xD;
          -  Any psychotic disorder or current psychiatric symptoms requiring specific attention,&#xD;
             including need for psychiatric medications for current major depression and anxiety&#xD;
             disorders.&#xD;
&#xD;
          -  Any significant current medical condition such as neurological, cardiovascular,&#xD;
             endocrine, renal, liver, thyroid pathology; subjects on medications for any medical&#xD;
             condition will be excluded.&#xD;
&#xD;
          -  Peri and post-menopausal women, and those with hysterectomies.&#xD;
&#xD;
          -  Pregnant and lactating women will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sara K Blaine, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Auburn University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Auburn University MRI Center</name>
      <address>
        <city>Auburn</city>
        <state>Alabama</state>
        <zip>36832</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>March 19, 2022</last_update_submitted>
  <last_update_submitted_qc>March 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Auburn University</investigator_affiliation>
    <investigator_full_name>Sara K Blaine</investigator_full_name>
    <investigator_title>Assistant Professsor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>HIPAA requirements prohibit sharing of individual data. De-identified group data will be available.</ipd_description>
  </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/NCT04412824
org study id: 19-263 MR 1907
secondary id: R00AA025401
nct id: NCT04412824
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study proposes to examine both the peripheral and central nervous system responses when
      light social drinkers and binge/heavy social drinkers are exposed to visual ethanol cues,
      followed by oral ethanol. The findings will provide a greater understanding of the brain
      mechanisms (cerebral blood flow and functional connectivity) underlying the association
      between stress, cortisol release, alcohol craving, and alcohol stimulant and sedative
      effects. This knowledge could be significant in developing new therapies for the treatment of
      alcoholism.
Results from the 2014 National Survey on Drug Use and Health show that 26% of adults in the
      US engaged in binge drinking in the past month (SAMHSA 2014). Why some people "mature out" of
      this behavior while others persist may be due to one's physiological response to binge
      drinking. No previous study has assessed whether disrupted cortisol and neural network
      responses to alcohol cues may drive the compulsive alcohol consumption seen in binge drinking
      individuals who do not yet have an AUD.

      The investigator will recruit beer drinking, non-smoking men and women ages 21-45 (N=80,
      equal gender) who are either moderate drinkers or binge/heavy drinkers for two neuroimaging
      and neuroendocrine assessments to determine if their "real world" drinking behavior, in a
      prospective one month follow up, can be predicted based upon the cortisol and neural network
      responses to alcohol cues (with a placebo control, counter-balanced and randomized). Finally,
      the influence of genetic variation in the FK506-binding protein 5 (FKBP5) gene, which
      regulates cortisol activity, on the cortisol and neural network responses to alcohol cues
      will be explored.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Change in Neural Blood Flow
time frame: During the Procedure: measurements taken at 10, 20, 30 and 45 minutes during the procedure.
description: Blood flow is measured in ml/100 grams/minute. The interpretation is that blood flow to that area indicates that region of the brain is responding to the visual alcohol or non-alcoholic beverage cues. Change in blood flow will be calculated as the change (and slope) of measurements taken at 10, 20, 30 and 45 minutes during the procedure.
measure: Change in Cortisol
time frame: Before Procedure to 125 minutes after the procedure.
description: The units for cortisol are micrograms/deciliter and the interpretation is that amount has been released into the blood stream from the HPA axis in response to alcohol or alcohol cues. Change in Cortisol will be calculated by taking the change (and slopes) of measurements at 45, 30 and 5 minutes prior to procedure and comparing it to measurements taken at 65, 95, 110, 125 minutes following the procedure.
measure: Drinking Behavior in daily experience outside of laboratory
time frame: Day after Procedure to 30 days after procedure.
description: A smartphone app will be used to collect 4 surveys a day for 30 days after completion of both arms. Multilevel modeling will be used to analyze patterns of drinking over time.
measure: Amount of Alcohol Consumed
time frame: Immediately after the procedure.
description: After exposure to alcoholic beverage and non-alcoholic beverage visual cues, quantity of alcohol consumed in a free choice test will be measured in milliliters.
measure: Changes in Alcohol Urges (AUQ)
time frame: Before Procedure to 125 minutes after the procedure.
description: The urge to consume alcohol will be measured using the Alcohol Urge Questionnaire (AUQ). The AUQ consists of 8 questions 8-56 total point distribution. The greater the total points, the greater the measured urge to consume alcohol. The change in alcohol urge will be assessed with the taking the change (and slopes) of measurements at 45, 30 and 5 minutes prior to procedure and comparing it to measurements taken at 65, 95, 110, 125 minutes following the procedure.
measure: Stress levels in daily experience outside of laboratory
time frame: Post follow-up procedure (30 days)
description: A smartphone app will be used to collect 4 surveys a day for 30 days after completion of both arms. Multilevel modeling will be used to analyze subjective experience of stress over time.
measure: Genetic Risk Factors (Single Nucleotide Polymorphisms; SNPs) Association with Cerebral Blood Flow, Craving, and Real world drinking and stress
time frame: Post follow up procedure (within 2 years after procedure)
description: One sample of whole blood will be obtained and analyzed for genomic associations with other outcome measures.
arm group label: Alcohol Beverage Cues
arm group type: Active Comparator
description: Participants will complete an MRI with alcohol beverage visual cues and oral alcohol session.
arm group label: Non-Alcoholic Beverage Cues
arm group type: Placebo Comparator
description: Participants will complete an MRI with non-alcoholic beverage cues and oral alcohol session.
intervention type: Drug
intervention name: Intravenous blood draw
description: In addition to the oral delivery, an IV line will be placed for the purpose of drawing blood during the MRI session
arm group label: Alcohol Beverage Cues
arm group label: Non-Alcoholic Beverage Cues
other name: Indwelling catheter for blood draws
criteria: 
gender: All
minimum age: 21 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sara K Blaine, PhD
role: Principal Investigator
affiliation: Auburn University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Auburn University
investigator full name: Sara K Blaine
investigator title: Assistant Professsor
mesh term: Alcoholism
sharing ipd: No
ipd description: HIPAA requirements prohibit sharing of individual data. De-identified group data will be available.