<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/NCT03764098</url>
  </required_header>
  <id_info>
    <org_study_id>2000023970</org_study_id>
    <secondary_id>P01AA027473</secondary_id>
    <secondary_id>U54AA027989</secondary_id>
    <nct_id>NCT03764098</nct_id>
  </id_info>
  <brief_title>Mechanistic Evaluation of Guanfacine on Drinking Behavior in Women and Men With Alcohol Use Disorders</brief_title>
  <official_title>Mechanistic Evaluation of Guanfacine on Drinking Behavior in Women and Men With Alcohol Use Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale 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>Yale 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>
      For this protocol, the investigators plan to collect pilot data to examine sex differences in&#xD;
      guanfacine's effect on 1) counteracting stress and stimulation based drinking behavior in the&#xD;
      laboratory and 2) improving clinical outcomes during a subsequent treatment phase.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a double blind, placebo controlled, parallel group design, which will compare&#xD;
      guanfacine (6mg/day ER) to placebo (0mg/day) in treatment seeking adults meeting criteria for&#xD;
      DSM V alcohol use disorders (160, 40 per med x sex cell).&#xD;
&#xD;
      Eligibility screening consists of an intake session and a physical exam. Subjects meeting&#xD;
      eligibility criteria will be randomized to 6mg/day ER guanfacine or matching placebo,&#xD;
      stratified by sex. Titration to steady state medication levels will occur over a 3 week&#xD;
      period (Weeks minus 3 to minus 1). Subjects will then complete three laboratory sessions&#xD;
      during Week 0 to evaluate ad lib consumption.&#xD;
&#xD;
      During each laboratory session, personalized imagery (within subject factor, stress,&#xD;
      stimulating, or neutral/relaxing, order balanced) will precede a 2 hour alcohol&#xD;
      self-administration period. Subjects will then begin a 6 week treatment phase (Week 1 to 6)&#xD;
      where medication is combined with a medical management platform delivered at weekly&#xD;
      appointments.&#xD;
&#xD;
      At the end of the treatment phase, medication will be tapered for 5 days, and a final follow&#xD;
      up evaluation will occur 1 and 3 months following the end of treatment. Primary outcome&#xD;
      measures include the number of drinks consumed during the three self-administration sessions,&#xD;
      and reduction in percent heavy days of drinking during treatment.&#xD;
&#xD;
      Adverse events are evaluated at each study appointment and will be tabulated. The date March&#xD;
      1, 2019 was used as the actual start date that was associated with the preliminary funding.&#xD;
      The study start date has been updated to reflect the beginning of the U54 grant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Anticipated">February 28, 2026</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2025</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Alcohol Consumption</measure>
    <time_frame>120 minutes</time_frame>
    <description>Means mls of alcohol consumed for guanfacine ER and placebo groups during 120 minute alcohol self administration sessions with personalized stress imagery vs stimulation imagery vs neutral imagery taking place as close to Week 0 of steady state as possible comparing females to males.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Alcohol Use</condition>
  <arm_group>
    <arm_group_label>Guanfacine ER</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Guanfacine extended release (6mg/day ER). Administered orally twice daily at 8:00 AM and 8:00 PM while titrating to the full dose. Titration schedule: Days 1-3 1mg/day; 0.5mg/dose, Days 4-6 2mg/day; 1mg/dose, Days 7-9 3mg/day; 1.5mg/dose, Days 10-12 4mg/day; 2mg/dose; Days 13-15 5mg/day; 2.5mg/dose and Days 16-23 6mg/day; 3mg/dose. Once at steady state, administration is orally once per day at 8:00 PM.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Administered orally twice a day at 8:00 AM and 8:00 PM Days 1-23, then orally once a day at 8:00 PM.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Guanfacine ER</intervention_name>
    <description>Guanfacine Extended Release (6mg/day ER)</description>
    <arm_group_label>Guanfacine ER</arm_group_label>
    <other_name>Intuniv</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 21 70;&#xD;
&#xD;
          2. Able to read and write English;&#xD;
&#xD;
          3. Meets DSM V criteria for current (past 6 months) alcohol use disorder or Drinking&#xD;
             criteria: Males Drinks more than 14 drinks per week and exceeds 4 drinks per day at&#xD;
             least twice per week; Females Drinks &gt; more than 7 drinks per week and exceeds 3&#xD;
             drinks per day at least twice per week. Must meet drinking criteria during a&#xD;
             consecutive 30 day period prior to baseline;&#xD;
&#xD;
          4. Laboratory sessions will be scheduled such that subjects will not have major&#xD;
             responsibilities on the following day which might limit drinking during the self&#xD;
             administration session (e.g., job interview, exam);&#xD;
&#xD;
          5. Able to take oral medications and willing to adhere to medication regimen;&#xD;
&#xD;
          6. indicate willingness to cut down on drinking during the treatment period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with any significant current medical conditions (neurological, cardiovascular&#xD;
             [including hypertension or hypotension: sitting BP more than 160/100 or less than&#xD;
             90/60mmHg at baseline screening], endocrine, thyroid, renal, liver), seizures,&#xD;
             delirium or hallucinations, or other unstable medical conditions including HIV;&#xD;
&#xD;
          2. Current DSM V substance use disorder, other than alcohol abuse disorder or nicotine&#xD;
             dependence;&#xD;
&#xD;
          3. A positive test result at intake appointment on urine drug screens conducted for&#xD;
             illicit drugs;&#xD;
&#xD;
          4. Past 30 day use of psychoactive drugs including anxiolytics and antidepressants;&#xD;
&#xD;
          5. Women who are pregnant or nursing, or fail to use one of the following methods of&#xD;
             birth control unless she or partner is surgically sterile or she is postmenopausal&#xD;
             (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive&#xD;
             sponge, double barrier [diaphragm or condom plus spermicide], or IUD);&#xD;
&#xD;
          6. Suicidal, homicidal or evidence of current (past 6 month) mental illness such as&#xD;
             schizophrenia, bipolar disorder or major depression, or anxiety disorders;&#xD;
&#xD;
          7. Meet DSM V criteria for current (past 6 month) ADHD;&#xD;
&#xD;
          8. Only one member per household can participate in the study&#xD;
&#xD;
          9. Specific exclusions for administration of guanfacine not already specified include:&#xD;
             EKG evidence at baseline screening of any clinically significant conduction&#xD;
             abnormalities or arrhythmias; known intolerance for guanfacine or any alpha blocker;&#xD;
             history of fainting, syncopal attacks, heart failure or myocardial infarction, or&#xD;
             impaired liver (AST, ALT &gt; 3x normal) or renal function (estimated creatinine&#xD;
             clearance &lt;60 cc/min); treatment with any antihypertensive drug or any alpha&#xD;
             adrenergic blocker; use of any CNS depressant (e.g., phenothiazines, barbiturates,&#xD;
             benzodiazepines);&#xD;
&#xD;
         10. Subjects likely to exhibit clinically significant alcohol withdrawal during the study.&#xD;
             Specifically, we will exclude subjects who a) have a history of perceptual&#xD;
             distortions, seizures, delirium, or hallucinations upon withdrawal, or b) have a score&#xD;
             of more than 8 on the Clinical Institute Withdrawal Assessment scale at intake&#xD;
             appointments;&#xD;
&#xD;
         11. Subjects who have taken any investigational drug within 4 weeks immediately preceding&#xD;
             admission to the treatment period;&#xD;
&#xD;
         12. Participation within the past 8 weeks in other studies that involve additive blood&#xD;
             sampling and/or interventional measures that would be considered excessive in&#xD;
             combination with the current application;&#xD;
&#xD;
         13. at intake express desire to completely abstain from alcohol;&#xD;
&#xD;
         14. currently in treatment for alcohol use&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sherry McKee, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Meaghan Lavery</last_name>
    <phone>203-737-2783</phone>
    <email>meaghan.lavery@yale.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sabrina Coppola</last_name>
    <phone>203-737-2827</phone>
    <email>sabrina.coppola@yale.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Meaghan Lavery</last_name>
      <phone>203-737-2783</phone>
      <email>meaghan.lavery@yale.edu</email>
    </contact>
    <contact_backup>
      <last_name>Sabrina Coppola</last_name>
      <phone>203-737-2827</phone>
      <email>sabrina.coppola@yale.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sherry McKee, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yale University</investigator_affiliation>
    <investigator_full_name>Sherry McKee</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
    <mesh_term>Drinking Behavior</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Guanfacine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03764098
org study id: 2000023970
secondary id: P01AA027473
secondary id: U54AA027989
nct id: NCT03764098
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
For this protocol, the investigators plan to collect pilot data to examine sex differences in
      guanfacine's effect on 1) counteracting stress and stimulation based drinking behavior in the
      laboratory and 2) improving clinical outcomes during a subsequent treatment phase.
This study is a double blind, placebo controlled, parallel group design, which will compare
      guanfacine (6mg/day ER) to placebo (0mg/day) in treatment seeking adults meeting criteria for
      DSM V alcohol use disorders (160, 40 per med x sex cell).

      Eligibility screening consists of an intake session and a physical exam. Subjects meeting
      eligibility criteria will be randomized to 6mg/day ER guanfacine or matching placebo,
      stratified by sex. Titration to steady state medication levels will occur over a 3 week
      period (Weeks minus 3 to minus 1). Subjects will then complete three laboratory sessions
      during Week 0 to evaluate ad lib consumption.

      During each laboratory session, personalized imagery (within subject factor, stress,
      stimulating, or neutral/relaxing, order balanced) will precede a 2 hour alcohol
      self-administration period. Subjects will then begin a 6 week treatment phase (Week 1 to 6)
      where medication is combined with a medical management platform delivered at weekly
      appointments.

      At the end of the treatment phase, medication will be tapered for 5 days, and a final follow
      up evaluation will occur 1 and 3 months following the end of treatment. Primary outcome
      measures include the number of drinks consumed during the three self-administration sessions,
      and reduction in percent heavy days of drinking during treatment.

      Adverse events are evaluated at each study appointment and will be tabulated. The date March
      1, 2019 was used as the actual start date that was associated with the preliminary funding.
      The study start date has been updated to reflect the beginning of the U54 grant.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Alcohol Consumption
time frame: 120 minutes
description: Means mls of alcohol consumed for guanfacine ER and placebo groups during 120 minute alcohol self administration sessions with personalized stress imagery vs stimulation imagery vs neutral imagery taking place as close to Week 0 of steady state as possible comparing females to males.
arm group label: Guanfacine ER
arm group type: Experimental
description: Guanfacine extended release (6mg/day ER). Administered orally twice daily at 8:00 AM and 8:00 PM while titrating to the full dose. Titration schedule: Days 1-3 1mg/day; 0.5mg/dose, Days 4-6 2mg/day; 1mg/dose, Days 7-9 3mg/day; 1.5mg/dose, Days 10-12 4mg/day; 2mg/dose; Days 13-15 5mg/day; 2.5mg/dose and Days 16-23 6mg/day; 3mg/dose. Once at steady state, administration is orally once per day at 8:00 PM.
arm group label: Placebo
arm group type: Placebo Comparator
description: Administered orally twice a day at 8:00 AM and 8:00 PM Days 1-23, then orally once a day at 8:00 PM.
intervention type: Drug
intervention name: Guanfacine ER
description: Guanfacine Extended Release (6mg/day ER)
arm group label: Guanfacine ER
other name: Intuniv
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sherry McKee, PhD
role: Principal Investigator
affiliation: Yale University
last name: Meaghan Lavery
phone: 203-737-2783
email: meaghan.lavery@yale.edu
last name: Sabrina Coppola
phone: 203-737-2827
email: sabrina.coppola@yale.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Yale University
investigator full name: Sherry McKee
investigator title: Professor
mesh term: Alcoholism
mesh term: Alcohol Drinking
mesh term: Drinking Behavior
mesh term: Guanfacine
sharing ipd: No