xml: <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/NCT06002633</url>
    </required_header>
    <id_info>
      <org_study_id>R01AA030740</org_study_id>
      <nct_id>NCT06002633</nct_id>
    </id_info>
    <brief_title>Approach-Avoidance and Alcohol Challenge Study in PTSD</brief_title>
    <acronym>PACS</acronym>
    <official_title>Alcohol, Approach-Avoidance, and Neurocircuitry Interactions in PTSD</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>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Individuals with posttraumatic stress disorder (PTSD) have greater prevalence of alcohol use&#xD;
        disorders (AUDs), with this comorbidity associated with worse illness outcomes, yet there&#xD;
        remains limited mechanistic understanding of how PTSD confers risk for AUD. Understanding&#xD;
        risk factors that associate with and predict the development of AUDs in PTSD could inform&#xD;
        interventions and prevention efforts to reduce the rate of this comorbidity and improve&#xD;
        outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in&#xD;
        PTSD aimed at capturing the mechanisms leading to the emergence of AUDs. There is growing&#xD;
        evidence PTSD is related to biased decision-making during approach-avoidance conflict.&#xD;
        Alcohol is also suggested to alter approach-avoidance decision-making. AUDs and acute alcohol&#xD;
        intoxication is associated with a bias to seek out reward despite the possibility of threat&#xD;
        (e.g., contributing to relapse following alcohol cue exposure and risky behavior during&#xD;
        intoxication respectively). Alcohol-induced changes in approach-avoidance decision-making&#xD;
        have not been investigated in the context of PTSD, but emerging data support the&#xD;
        investigators' hypothesis that an interaction between alcohol and approach-avoidance conflict&#xD;
        in PTSD may occur and contribute to risk for alcohol misuse and development of alcohol&#xD;
        problems. No current data, cross-sectional or longitudinal, have tested the role of&#xD;
        alcohol-induced changes in approach-avoidance conflict as a mechanism of risk for AUD among&#xD;
        individuals with PTSD. To address this gap, the investigators propose to leverage the group's&#xD;
        expertise in placebo-controlled alcohol administration procedures, longitudinal modeling,&#xD;
        functional neuroimaging, and computational neuroscience approaches to investigate the effects&#xD;
        of acute alcohol on approach-avoidance decision-making and mediating changes in multivariate&#xD;
        neurocircuitry patterns in limbic, striatal, and salience networks.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The proposed study will test the conceptual model positing that acute alcohol alters the&#xD;
        relative bias in computational mechanisms for threat vs reward, thereby decreasing avoidance&#xD;
        to threat and increasing approach to reward in adults with PTSD, and through this mechanism&#xD;
        increases risk for heavier alcohol use over time. Research aims are to identify&#xD;
        alcohol-induced changes in approach-avoidance decision-making and mediating neural networks&#xD;
        that predict alcohol use and symptoms of AUDs over a one-year follow-up period in adults with&#xD;
        PTSD, compared to adults with interpersonal violence exposure but no PTSD and healthy&#xD;
        comparison adults. Essential to successfully improving clinical prognosis in PTSD are&#xD;
        research results that enable better prediction, diagnosis, and treatment based on the&#xD;
        individual. There is a paucity of human clinical research investigating interactions between&#xD;
        acute alcohol exposure and PTSD that may drive risk for development of AUDs following trauma.&#xD;
        Data could identify brain and behavioral mechanisms explaining how alcohol alters an&#xD;
        important domain of PTSD contributing to risk for alcohol misuse and development of alcohol&#xD;
        problems. Results could pave way for development of novel behavioral and pharmacological&#xD;
        methods to treat PTSD and decrease risk for developing comorbid AUDs.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">May 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2028</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>Crossover Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>ratio of approach to avoidance choices</measure>
      <time_frame>1 week</time_frame>
      <description>the number of trials on which individuals chose to avoid vs approach will be quantified during the task and compared between placebo and alcohol conditions</description>
    </primary_outcome>
    <primary_outcome>
      <measure>changes in dorsal anterior cingulate cortex activation</measure>
      <time_frame>1 week</time_frame>
      <description>the degree of activation on high conflict trials (relative to low conflict trials) on the task in the dorsal anterior cingulate will be quantified and compared between the placebo and alcohol conditions</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Relations between ratio of approach to avoidance choices with alcohol use over a one-year follow-up</measure>
      <time_frame>1 year</time_frame>
      <description>The relationship between the number of trials on which individuals chose to avoid vs approach during the alcohol session with alcohol use over a one-year follow up will be modeled. Number of drinks consumed per day over the course of the follow-up year will be used to calculate Area Under the Curve (AUC), with AUC as the dependent variable.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Relations between changes in dorsal anterior cingulate cortex activation with alcohol use over a one-year follow-up</measure>
      <time_frame>1 year</time_frame>
      <description>The relationship between the degree of activation on high conflict trials (relative to low conflict trials) on the task in the dorsal anterior cingulate during the alcohol session with alcohol use over a one-year follow up will be modeled. Number of drinks consumed per day over the course of the follow-up year will be used to calculate Area Under the Curve (AUC), with AUC as the dependent variable.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Post-Traumatic Stress Disorder</condition>
    <condition>Alcohol Drinking</condition>
    <arm_group>
      <arm_group_label>Alcohol</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will drink beverages containing alcohol.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will drink beverages containing a very low dose of alcohol (placebo condition).</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Alcohol</intervention_name>
      <description>Participants will consume beverages containing alcohol.</description>
      <arm_group_label>Alcohol</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Participants will consume beverages containing a very low dose of alcohol (placebo condition).</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          1. Inclusion criteria for all participants:&#xD;
  &#xD;
                 -  between 21 and 60 years of age&#xD;
  &#xD;
                 -  having consumed at least 4 (men) or 3 (women) drinks on at least two occasions&#xD;
                    over the last year&#xD;
  &#xD;
            2. Inclusion criteria for PTSD participants:&#xD;
  &#xD;
               - Meeting diagnostic criteria for PTSD, confirmed by structured interview&#xD;
  &#xD;
            3. For all subjects exclusion criteria include:&#xD;
  &#xD;
                 -  history of significant medical illness, particularly if possible changes in&#xD;
                    cerebral tissue&#xD;
  &#xD;
                 -  neurologic abnormality including significant head trauma (loss of consciousness&#xD;
                    of ≥5-min)&#xD;
  &#xD;
                 -  full Scale IQ &lt;85&#xD;
  &#xD;
                 -  contraindication to MRI scanning&#xD;
  &#xD;
                 -  positive pregnancy test&#xD;
  &#xD;
                 -  current alcohol or substance use disorder&#xD;
  &#xD;
                 -  scores &gt; 15 on the alcohol Use Disorders Identification Test (AUDIT; part of&#xD;
                    phone screen)&#xD;
  &#xD;
                 -  ever being in an abstinence-oriented treatment program for alcohol use&#xD;
  &#xD;
                 -  reporting wanting to quit drinking but not being able to&#xD;
  &#xD;
                 -  any medical, religious, or other reasons for not drinking alcohol&#xD;
  &#xD;
                 -  history of heart attack, heart trouble, high blood pressure, diabetes, or liver&#xD;
                    disease&#xD;
  &#xD;
                 -  an adverse reaction to alcoholic beverages&#xD;
  &#xD;
                 -  reporting never consuming 4 (men) or 3 (women) or more drinks on at least two&#xD;
                    occasions over the last year&#xD;
  &#xD;
                 -  unwillingness to have a friend or family member drive them home after the alcohol&#xD;
                    administration sessions&#xD;
  &#xD;
            4. Additional exclusion criteria for participants in PTSD and IPV-exposed but no PTSD&#xD;
               groups:&#xD;
  &#xD;
                 -  not taking medications for &gt;4 weeks (i.e. participants must be stable on meds)&#xD;
  &#xD;
                 -  acute suicidality with intent&#xD;
  &#xD;
                 -  history of bipolar/psychotic disorder or OCD&#xD;
  &#xD;
            5. Additional exclusion criteria for participants in IPV-exposure but no PTSD group:&#xD;
  &#xD;
               - history of PTSD, current mental health disorders&#xD;
  &#xD;
            6. Additional exclusion criteria for healthy comparison subjects also include:&#xD;
  &#xD;
                 -  any prior psychiatric hospitalizations&#xD;
  &#xD;
                 -  lifetime history of a neurodevelopmental disorder, affective disorder, psychotic&#xD;
                    disorder, suicide attempt, or eating disorder&#xD;
  &#xD;
                 -  greater than 1 month of lifetime psychotropic medication&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Elizabeth Lippard, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Texas at Austin</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Josh Cisler, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Texas at Austin</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Research Coordinator</last_name>
      <phone>5124955198</phone>
      <email>behavioral.neuroimaging@austin.utexas.edu</email>
    </overall_contact>
    <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>
      <contact>
        <last_name>Research Coordinator</last_name>
        <phone>512-495-5198</phone>
        <email>behavioral.neuroimaging@austin.utexas.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Texas at Austin</investigator_affiliation>
      <investigator_full_name>Elizabeth Thomas Cox Lippard</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Stress Disorders, Traumatic</mesh_term>
      <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
      <mesh_term>Alcohol Drinking</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>After study completion and publication of finding, functional neuroimaging data and behavior data collected following alcohol and placebo conditions will be shared.</ipd_description>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>We will complete all our analyses and publish results and methodologies in scientific journals before the data are available to the research community. Data will be made available following 6 months after publication.</ipd_time_frame>
      <ipd_access_criteria>We will be collecting identifying information. Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06002633
  org study id: R01AA030740
  nct id: NCT06002633
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Individuals with posttraumatic stress disorder (PTSD) have greater prevalence of alcohol use
        disorders (AUDs), with this comorbidity associated with worse illness outcomes, yet there
        remains limited mechanistic understanding of how PTSD confers risk for AUD. Understanding
        risk factors that associate with and predict the development of AUDs in PTSD could inform
        interventions and prevention efforts to reduce the rate of this comorbidity and improve
        outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in
        PTSD aimed at capturing the mechanisms leading to the emergence of AUDs. There is growing
        evidence PTSD is related to biased decision-making during approach-avoidance conflict.
        Alcohol is also suggested to alter approach-avoidance decision-making. AUDs and acute alcohol
        intoxication is associated with a bias to seek out reward despite the possibility of threat
        (e.g., contributing to relapse following alcohol cue exposure and risky behavior during
        intoxication respectively). Alcohol-induced changes in approach-avoidance decision-making
        have not been investigated in the context of PTSD, but emerging data support the
        investigators' hypothesis that an interaction between alcohol and approach-avoidance conflict
        in PTSD may occur and contribute to risk for alcohol misuse and development of alcohol
        problems. No current data, cross-sectional or longitudinal, have tested the role of
        alcohol-induced changes in approach-avoidance conflict as a mechanism of risk for AUD among
        individuals with PTSD. To address this gap, the investigators propose to leverage the group's
        expertise in placebo-controlled alcohol administration procedures, longitudinal modeling,
        functional neuroimaging, and computational neuroscience approaches to investigate the effects
        of acute alcohol on approach-avoidance decision-making and mediating changes in multivariate
        neurocircuitry patterns in limbic, striatal, and salience networks.
  The proposed study will test the conceptual model positing that acute alcohol alters the
        relative bias in computational mechanisms for threat vs reward, thereby decreasing avoidance
        to threat and increasing approach to reward in adults with PTSD, and through this mechanism
        increases risk for heavier alcohol use over time. Research aims are to identify
        alcohol-induced changes in approach-avoidance decision-making and mediating neural networks
        that predict alcohol use and symptoms of AUDs over a one-year follow-up period in adults with
        PTSD, compared to adults with interpersonal violence exposure but no PTSD and healthy
        comparison adults. Essential to successfully improving clinical prognosis in PTSD are
        research results that enable better prediction, diagnosis, and treatment based on the
        individual. There is a paucity of human clinical research investigating interactions between
        acute alcohol exposure and PTSD that may drive risk for development of AUDs following trauma.
        Data could identify brain and behavioral mechanisms explaining how alcohol alters an
        important domain of PTSD contributing to risk for alcohol misuse and development of alcohol
        problems. Results could pave way for development of novel behavioral and pharmacological
        methods to treat PTSD and decrease risk for developing comorbid AUDs.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: ratio of approach to avoidance choices
  time frame: 1 week
  description: the number of trials on which individuals chose to avoid vs approach will be quantified during the task and compared between placebo and alcohol conditions
  measure: changes in dorsal anterior cingulate cortex activation
  time frame: 1 week
  description: the degree of activation on high conflict trials (relative to low conflict trials) on the task in the dorsal anterior cingulate will be quantified and compared between the placebo and alcohol conditions
  measure: Relations between ratio of approach to avoidance choices with alcohol use over a one-year follow-up
  time frame: 1 year
  description: The relationship between the number of trials on which individuals chose to avoid vs approach during the alcohol session with alcohol use over a one-year follow up will be modeled. Number of drinks consumed per day over the course of the follow-up year will be used to calculate Area Under the Curve (AUC), with AUC as the dependent variable.
  measure: Relations between changes in dorsal anterior cingulate cortex activation with alcohol use over a one-year follow-up
  time frame: 1 year
  description: The relationship between the degree of activation on high conflict trials (relative to low conflict trials) on the task in the dorsal anterior cingulate during the alcohol session with alcohol use over a one-year follow up will be modeled. Number of drinks consumed per day over the course of the follow-up year will be used to calculate Area Under the Curve (AUC), with AUC as the dependent variable.
  arm group label: Alcohol
  arm group type: Active Comparator
  description: Participants will drink beverages containing alcohol.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Participants will drink beverages containing a very low dose of alcohol (placebo condition).
  intervention type: Other
  intervention name: Alcohol
  description: Participants will consume beverages containing alcohol.
  arm group label: Alcohol
  intervention type: Other
  intervention name: Placebo
  description: Participants will consume beverages containing a very low dose of alcohol (placebo condition).
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Elizabeth Lippard, PhD
  role: Principal Investigator
  affiliation: University of Texas at Austin
  last name: Josh Cisler, PhD
  role: Principal Investigator
  affiliation: University of Texas at Austin
  last name: Research Coordinator
  phone: 5124955198
  email: behavioral.neuroimaging@austin.utexas.edu
  facility: 
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Texas at Austin
  investigator full name: Elizabeth Thomas Cox Lippard
  investigator title: Assistant Professor
  mesh term: Stress Disorders, Traumatic
  mesh term: Stress Disorders, Post-Traumatic
  mesh term: Alcohol Drinking
  sharing ipd: Yes
  ipd description: After study completion and publication of finding, functional neuroimaging data and behavior data collected following alcohol and placebo conditions will be shared.
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: We will complete all our analyses and publish results and methodologies in scientific journals before the data are available to the research community. Data will be made available following 6 months after publication.
  ipd access criteria: We will be collecting identifying information. Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.