<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/NCT03827460</url>
  </required_header>
  <id_info>
    <org_study_id>1809467722</org_study_id>
    <nct_id>NCT03827460</nct_id>
  </id_info>
  <brief_title>Sex Differences in the Response to Abstinence From Alcohol.</brief_title>
  <acronym>SPAR</acronym>
  <official_title>Sex Differences in the Response to Abstinence From Alcohol.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      In laboratory animals, repeated cycles of abstinence from and return to alcohol drinking can&#xD;
      lead to changes in alcohol intake. In a study of the effect of abstinence on drinking in&#xD;
      humans, the investigators found evidence that abstinence affects drinking differently in&#xD;
      women compared to men. In the present study, the investigators propose to study how men and&#xD;
      women respond to abstinence, and whether this information can be used to improve intervention&#xD;
      and prevention strategies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Women and men differ in how quickly they progress from social to problematic alcohol&#xD;
      drinking. In laboratory animals, short-term abstinence increases alcohol consumption, with&#xD;
      repeated deprivations leading to disordered drinking. In a preliminary study, the&#xD;
      investigators found that men and women differed in how their motivation to drink alcohol&#xD;
      changed after a short period of abstinence. The investigators hypothesize that this&#xD;
      difference may affect their transition to alcohol use disorders. The objectives of this&#xD;
      application are to characterize the human post abstinence response, and use identical alcohol&#xD;
      exposures to study the mechanisms underlying identified sex differences. In addition, the&#xD;
      investigators will complete a 2 year prospective study of natural drinking patterns to assess&#xD;
      how self-reported abstinence intervals influence drinking trajectories. The long-term goal of&#xD;
      this project is to inform alcohol use disorder treatment and to design and test novel&#xD;
      interventions using the laboratory model of post-abstinence response. There is a critical&#xD;
      unfilled need to understand sex differences in disease progression, and this lab-based&#xD;
      assessment coupled to longitudinal follow-up provides the rigorous experimental design to&#xD;
      begin to meet that need. This project will increase scientific knowledge by advancing the&#xD;
      translation between preclinical and clinical models, eventually informing sex-specific&#xD;
      intervention and prevention strategies for problematic drinking and establishing a model to&#xD;
      test those interventions..&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 10, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</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>
    <intervention_model_description>Arms 1 and 2: 2 session parallel, random order, no blind.&#xD;
Arm 3: Sequential, includes all subjects who complete Arm1 or Arm 2</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>The intervention is 2 weeks of monitored abstinence from alcohol compared to usual drinking. Thus, it is not possible to mask conditions for participants or investigators.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Sex differences in the effect of abstinence on alcohol self-administration.</measure>
    <time_frame>2 single day laboratory sessions, one following 2 weeks alcohol abstinence</time_frame>
    <description>The effect of 2 weeks abstinence on intravenous alcohol intake will be compared in men and women.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sex differences in the effect of abstinence on sensitivity of the P3 response to alcohol.</measure>
    <time_frame>2 single day laboratory sessions, one following 2 weeks alcohol abstinence</time_frame>
    <description>The effect of 2 weeks abstinence from alcohol on sensitivity of the neurophysiological P3 response to alcohol, assessed using a stop-signal response task, will be compared in women and men during an iv infusion clamp.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sex differences in the effect of abstinence on subjective responses to alcohol.</measure>
    <time_frame>2 single day laboratory sessions, one following 2 weeks alcohol abstinence</time_frame>
    <description>The effect of 2 weeks abstinence from alcohol on subjective responses to alcohol in women and men will be assessed using a survey during an iv infusion clamp.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The role of changes in alcohol elimination on sex differences in response to abstinence.</measure>
    <time_frame>2 single day laboratory sessions, one following 2 weeks alcohol abstinence</time_frame>
    <description>The effect of 2 weeks abstinence from alcohol on alcohol elimination in men and women will be assessed using an iv alcohol infusion clamp.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response to abstinence as a predictor of alcohol risk in women and men.</measure>
    <time_frame>2 years</time_frame>
    <description>For both Arm 1 and Arm 2, daily alcohol consumption will be surveyed every 2 months for 2 years following the laboratory sessions. Self-imposed periods of abstinence will be assessed to determine if subsequent daily alcohol intake increases or decreases, and to determine if men and women differ in the effect of abstinence on drinking.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Free access alcohol self-administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the 2.5-hour free-access self-administration sessions, the participant may choose to complete a task for an alcohol or water reward. Interventions include Abstinence from Alcohol and Usual Drinking</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clamped alcohol exposure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A battery of behavioral tasks will be administered to participants before, and at the beginning and end of a 3 hour clamped exposure to alcohol (fixed at 80 mg/dL). EEG will be recorded throughout to assess event related potentials associated with task performance. Interventions include Abstinence from Alcohol and Usual Drinking.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2 year followup</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants from both Arm 1 and Arm 2 will be surveyed every 2 months for alcohol consumption for 2 years following the Experimental phase. Interventions include Abstinence from Alcohol and Usual Drinking.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Abstinence from alcohol</intervention_name>
    <description>Participants will undergo a laboratory alcohol infusion session that terminates 2 weeks of monitored abstinence from alcohol</description>
    <arm_group_label>2 year followup</arm_group_label>
    <arm_group_label>Clamped alcohol exposure</arm_group_label>
    <arm_group_label>Free access alcohol self-administration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Usual drinking</intervention_name>
    <description>Participants will undergo a laboratory alcohol infusion session during a period of usual drinking behavior</description>
    <arm_group_label>2 year followup</arm_group_label>
    <arm_group_label>Clamped alcohol exposure</arm_group_label>
    <arm_group_label>Free access alcohol self-administration</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Moderate social drinkers&#xD;
&#xD;
          -  Able to understand/complete questionnaires and procedures in English&#xD;
&#xD;
          -  Body mass index (BMI) between 18.5 and 32 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Desire to be treated for any substance use disorder or court ordered to not drink&#xD;
             alcohol&#xD;
&#xD;
          -  Medical disorders or other conditions such as alcohol withdrawal seizures or delirium&#xD;
             tremens that may influence study outcome or participant safety&#xD;
&#xD;
          -  Medications (past 30 days) that could influence data or participant safety (e.g.&#xD;
             antidepressants, antipsychotics, benzodiazepines, etc.) as determined by investigators&#xD;
&#xD;
          -  DSM 5 Disorders (non AUD) or current/history of neurological disease of cerebral&#xD;
             origin, or head injury with &gt; 20 min loss of consciousness&#xD;
&#xD;
          -  Positive breath alcohol reading on arrival at any study visit&#xD;
&#xD;
          -  Actively suicidal (for example, any suicide attempts within the past year or any&#xD;
             current suicidal intent, including a plan) or are at serious suicidal risk, by&#xD;
             clinical judgment of the investigator&#xD;
&#xD;
          -  Any condition for which the principal investigators determine it is unsafe or not&#xD;
             prudent to enroll&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martin H Plawecki, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Psychiatry, Indiana University School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melissa A Cyders, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Psychology, Indiana University-Purdue University at Indianapolis</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ann E Kosobud, Ph.D.</last_name>
    <phone>(317) 274-0087</phone>
    <email>akosobud@iupui.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Study Recruiter</last_name>
      <phone>317-948-6551</phone>
      <email>erptest@iupui.edu</email>
    </contact>
    <investigator>
      <last_name>Martin H Plawecki, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Melissa A Cyders, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wei Wu, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>May 18, 2023</last_update_submitted>
  <last_update_submitted_qc>May 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Martin Plawecki</investigator_full_name>
    <investigator_title>Assistant Professor of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>Alcohol</keyword>
  <keyword>Alcoholism</keyword>
  <keyword>Sex Differences</keyword>
  <keyword>Abstinence</keyword>
  <keyword>Alcohol Deprivation Effect</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The final raw dataset will be available to other researchers when we have collected all subjects and completed our own planned analyses. Prior to completion of our own planned analyses, we would be willing to consider releasing the dataset upon request. We will work with our IRB to establish a strategy for de-identifying the data while retaining the ability to ensure the quality of the stored data, and develop a data-sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>After all subjects have been collected and the primary outcomes accepted for publication. The dataset will be available indefinitely,</ipd_time_frame>
    <ipd_access_criteria>On request to the PIs</ipd_access_criteria>
  </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/NCT03827460
org study id: 1809467722
nct id: NCT03827460
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In laboratory animals, repeated cycles of abstinence from and return to alcohol drinking can
      lead to changes in alcohol intake. In a study of the effect of abstinence on drinking in
      humans, the investigators found evidence that abstinence affects drinking differently in
      women compared to men. In the present study, the investigators propose to study how men and
      women respond to abstinence, and whether this information can be used to improve intervention
      and prevention strategies.
Women and men differ in how quickly they progress from social to problematic alcohol
      drinking. In laboratory animals, short-term abstinence increases alcohol consumption, with
      repeated deprivations leading to disordered drinking. In a preliminary study, the
      investigators found that men and women differed in how their motivation to drink alcohol
      changed after a short period of abstinence. The investigators hypothesize that this
      difference may affect their transition to alcohol use disorders. The objectives of this
      application are to characterize the human post abstinence response, and use identical alcohol
      exposures to study the mechanisms underlying identified sex differences. In addition, the
      investigators will complete a 2 year prospective study of natural drinking patterns to assess
      how self-reported abstinence intervals influence drinking trajectories. The long-term goal of
      this project is to inform alcohol use disorder treatment and to design and test novel
      interventions using the laboratory model of post-abstinence response. There is a critical
      unfilled need to understand sex differences in disease progression, and this lab-based
      assessment coupled to longitudinal follow-up provides the rigorous experimental design to
      begin to meet that need. This project will increase scientific knowledge by advancing the
      translation between preclinical and clinical models, eventually informing sex-specific
      intervention and prevention strategies for problematic drinking and establishing a model to
      test those interventions..
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Arms 1 and 2: 2 session parallel, random order, no blind.
Arm 3: Sequential, includes all subjects who complete Arm1 or Arm 2
primary purpose: Basic Science
masking: None (Open Label)
masking description: The intervention is 2 weeks of monitored abstinence from alcohol compared to usual drinking. Thus, it is not possible to mask conditions for participants or investigators.
measure: Sex differences in the effect of abstinence on alcohol self-administration.
time frame: 2 single day laboratory sessions, one following 2 weeks alcohol abstinence
description: The effect of 2 weeks abstinence on intravenous alcohol intake will be compared in men and women.
measure: Sex differences in the effect of abstinence on sensitivity of the P3 response to alcohol.
time frame: 2 single day laboratory sessions, one following 2 weeks alcohol abstinence
description: The effect of 2 weeks abstinence from alcohol on sensitivity of the neurophysiological P3 response to alcohol, assessed using a stop-signal response task, will be compared in women and men during an iv infusion clamp.
measure: Sex differences in the effect of abstinence on subjective responses to alcohol.
time frame: 2 single day laboratory sessions, one following 2 weeks alcohol abstinence
description: The effect of 2 weeks abstinence from alcohol on subjective responses to alcohol in women and men will be assessed using a survey during an iv infusion clamp.
measure: The role of changes in alcohol elimination on sex differences in response to abstinence.
time frame: 2 single day laboratory sessions, one following 2 weeks alcohol abstinence
description: The effect of 2 weeks abstinence from alcohol on alcohol elimination in men and women will be assessed using an iv alcohol infusion clamp.
measure: Response to abstinence as a predictor of alcohol risk in women and men.
time frame: 2 years
description: For both Arm 1 and Arm 2, daily alcohol consumption will be surveyed every 2 months for 2 years following the laboratory sessions. Self-imposed periods of abstinence will be assessed to determine if subsequent daily alcohol intake increases or decreases, and to determine if men and women differ in the effect of abstinence on drinking.
arm group label: Free access alcohol self-administration
arm group type: Experimental
description: During the 2.5-hour free-access self-administration sessions, the participant may choose to complete a task for an alcohol or water reward. Interventions include Abstinence from Alcohol and Usual Drinking
arm group label: Clamped alcohol exposure
arm group type: Experimental
description: A battery of behavioral tasks will be administered to participants before, and at the beginning and end of a 3 hour clamped exposure to alcohol (fixed at 80 mg/dL). EEG will be recorded throughout to assess event related potentials associated with task performance. Interventions include Abstinence from Alcohol and Usual Drinking.
arm group label: 2 year followup
arm group type: Experimental
description: Participants from both Arm 1 and Arm 2 will be surveyed every 2 months for alcohol consumption for 2 years following the Experimental phase. Interventions include Abstinence from Alcohol and Usual Drinking.
intervention type: Behavioral
intervention name: Abstinence from alcohol
description: Participants will undergo a laboratory alcohol infusion session that terminates 2 weeks of monitored abstinence from alcohol
arm group label: 2 year followup
arm group label: Clamped alcohol exposure
arm group label: Free access alcohol self-administration
intervention type: Behavioral
intervention name: Usual drinking
description: Participants will undergo a laboratory alcohol infusion session during a period of usual drinking behavior
arm group label: 2 year followup
arm group label: Clamped alcohol exposure
arm group label: Free access alcohol self-administration
criteria: 
gender: All
minimum age: 21 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Martin H Plawecki, MD, PhD
role: Principal Investigator
affiliation: Psychiatry, Indiana University School of Medicine
last name: Melissa A Cyders, PhD
role: Principal Investigator
affiliation: Psychology, Indiana University-Purdue University at Indianapolis
last name: Ann E Kosobud, Ph.D.
phone: (317) 274-0087
email: akosobud@iupui.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Martin Plawecki
investigator title: Assistant Professor of Psychiatry
mesh term: Alcoholism
sharing ipd: Yes
ipd description: The final raw dataset will be available to other researchers when we have collected all subjects and completed our own planned analyses. Prior to completion of our own planned analyses, we would be willing to consider releasing the dataset upon request. We will work with our IRB to establish a strategy for de-identifying the data while retaining the ability to ensure the quality of the stored data, and develop a data-sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: After all subjects have been collected and the primary outcomes accepted for publication. The dataset will be available indefinitely,
ipd access criteria: On request to the PIs