<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/NCT03035708</url>
  </required_header>
  <id_info>
    <org_study_id>HLAB 001</org_study_id>
    <nct_id>NCT03035708</nct_id>
  </id_info>
  <brief_title>Human Laboratory Study of Varenicline for Alcohol Use Disorder</brief_title>
  <official_title>Human Laboratory Study of Varenicline for Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</source>
  <oversight_info>
    <has_dmc>No</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 is a double-blind, randomized, placebo-controlled, parallel group, two-site study&#xD;
      designed to assess the effects of varenicline as compared with placebo on responses to in&#xD;
      vivo alcohol cue exposure in the human laboratory setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study&#xD;
      designed to assess the effects of varenicline as compared with placebo on responses to in&#xD;
      vivo alcohol cue exposure in the human laboratory setting. After signing informed consent,&#xD;
      subjects will be screened for eligibility including medical history, physical examination,&#xD;
      vital signs, electrocardiogram (ECG), drinking history by the timeline follow-back (TLFB)&#xD;
      method, alcohol breathalyzer test, Clinical Institute Withdrawal Assessment for&#xD;
      Alcohol-revised (CIWA), medication use, MINI neuropsychiatric interview, urine toxicology&#xD;
      screen, clinical chemistry, response to cue reactivity, and Columbia Suicide Severity Rating&#xD;
      Scale (CSSR-S). Women of child-bearting potential will have a pregnancy test. If eligible for&#xD;
      the study, subjects will be randomized using a stratified permuted block randomization&#xD;
      procedure in an approximate 1:1 ratio (targeting 24 subjects per group - 12 subjects per&#xD;
      group per site) to receive either varenicline or placebo for 6 weeks. Any nicotine use versus&#xD;
      no use (cigarettes, cigars, chewing tobacco, electronic cigarettes, etc.) in the week before&#xD;
      randomization is the stratification variable.&#xD;
&#xD;
      Varenicline or matched placebo will be titrated over the first week of the study up the&#xD;
      maintenance dose of 1 mg (active) or two capsules (placebo) taken orally BID for an&#xD;
      additional 5 weeks. Subjects will be seen in the clinic at screening, at randomization and 6&#xD;
      other times during the study. A final follow-up telephone interview will occur during Week 9&#xD;
      (2 weeks after the end of study visit).&#xD;
&#xD;
      After the first two weeks and after five weeks of investigational product administration at&#xD;
      Study Week 3 and Study Week 6, respectively, subjects will undergo a cue reactivity paradigm&#xD;
      session (HLAB) including 4 individual visual analog scale (VAS) items assessing alcohol&#xD;
      craving, 2 VAS items assessing emotional reactivity to picture stimuli, and 2 items assessing&#xD;
      emotional manipulation. Immediately after the HLAB session, subjects will view each picture&#xD;
      again and record the emotion felt using the Self-Manikin Assessment (SAM).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Actual">July 7, 2018</completion_date>
  <primary_completion_date type="Actual">July 1, 2018</primary_completion_date>
  <phase>Phase 1/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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cue-elicited Craving</measure>
    <time_frame>Study Week 3</time_frame>
    <description>The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Heavy Drinking Days</measure>
    <time_frame>Weeks 3-6</time_frame>
    <description>The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6).</measure>
    <time_frame>Weeks 3-6</time_frame>
    <description>The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cigarettes Smoked Per Week</measure>
    <time_frame>Weeks 3-6</time_frame>
    <description>The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Penn Alcohol Craving Scale</measure>
    <time_frame>Study Weeks 3, 4, 5, 6 (assessed weekly during this period)</time_frame>
    <description>Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>varenicline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 mg BID (2 capsules BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 mg BID (2 capsules BID)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline</intervention_name>
    <description>1 mg BID</description>
    <arm_group_label>varenicline</arm_group_label>
    <other_name>Chantix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>1 mg BID</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        To be eligible, the subject must:&#xD;
&#xD;
          -  Be at least 21 years of age.&#xD;
&#xD;
          -  Meet the DSM 5 criteria for alcohol use disorder of a least moderate severity&#xD;
             (AUD-MS).&#xD;
&#xD;
          -  Be seeking treatment for AUD and desire a reduction or cessation of drinking.&#xD;
&#xD;
          -  Be able to verbalize an understanding of the consent form, able to provide written&#xD;
             informed consent, verbalize willingness to complete study procedures, able to&#xD;
             understand written and oral instructions in English and able to complete the&#xD;
             questionnaires required by the protocol.&#xD;
&#xD;
          -  Agree (if the subject is female and of child bearing potential) to use at least one of&#xD;
             the following methods of birth control, unless she is surgically sterile, partner is&#xD;
             surgically sterile or she is postmenopausal:&#xD;
&#xD;
               1. oral contraceptives,&#xD;
&#xD;
               2. contraceptive sponge,&#xD;
&#xD;
               3. patch,&#xD;
&#xD;
               4. double barrier (diaphragm/spermicidal or condom/spermicidal),&#xD;
&#xD;
               5. intrauterine contraceptive system,&#xD;
&#xD;
               6. levonorgestrel implant,&#xD;
&#xD;
               7. medroxyprogesterone acetate contraceptive injection,&#xD;
&#xD;
               8. complete abstinence from sexual intercourse, and/or&#xD;
&#xD;
               9. hormonal vaginal contraceptive ring.&#xD;
&#xD;
          -  Be able to take oral medication and be willing to adhere to the medication regimen.&#xD;
&#xD;
          -  Complete all assessments required at screening and baseline.&#xD;
&#xD;
          -  Have a place to live in the 2 weeks prior to randomization and not be at risk that&#xD;
             s/he will lose his/her housing in the next 2 months.&#xD;
&#xD;
          -  Not anticipate any significant problems with transportation arrangements or available&#xD;
             time to travel to the study site over the next 2 months.&#xD;
&#xD;
          -  Not have any unresolved legal problems that could jeopardize continuation or&#xD;
             completion of the study.&#xD;
&#xD;
          -  And others.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contact site for additional information&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raye Litten, PhD</last_name>
    <role>Study Director</role>
    <affiliation>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brown University</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <results_first_submitted>August 30, 2019</results_first_submitted>
  <results_first_submitted_qc>October 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 23, 2019</results_first_posted>
  <last_update_submitted>October 22, 2019</last_update_submitted>
  <last_update_submitted_qc>October 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Varenicline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 3, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03035708/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Varenicline</title>
          <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Varenicline</title>
          <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="23"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.4" spread="11.0"/>
                    <measurement group_id="B2" value="43.1" spread="12.1"/>
                    <measurement group_id="B3" value="43.7" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/ethnicity</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Drinks per day</title>
          <description>Drinks per day is computed by summing the number of standard drinks consumed during the period of interest divided by the number of days in the period of interest.</description>
          <units>drinks/day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.9" spread="2.4"/>
                    <measurement group_id="B2" value="7.6" spread="2.7"/>
                    <measurement group_id="B3" value="7.3" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Drinking per drinking day</title>
          <description>Drinks per drinking day is computed by summing the number of standard drinks consumed during the period of interest divided by the number of drinking days in the period of interest (i.e., days where the subject drank &gt;0 drinks). This measure differs from the measure, drinks per day, only in the denominator (drinks per day includes all days in the period of interest).</description>
          <units>drinks/drinking day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.5" spread="4.1"/>
                    <measurement group_id="B2" value="9.3" spread="5.2"/>
                    <measurement group_id="B3" value="8.9" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percent days abstinent</title>
          <units>percent days abstinent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15.1" spread="16.9"/>
                    <measurement group_id="B2" value="11.8" spread="15.9"/>
                    <measurement group_id="B3" value="13.4" spread="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percent heavy drinking days</title>
          <units>percent heavy drinking days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.3" spread="26.5"/>
                    <measurement group_id="B2" value="71.9" spread="24.3"/>
                    <measurement group_id="B3" value="69.2" spread="25.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Penn Alcohol Craving Scale (PACS) score</title>
          <description>The PACS is a five-item self-administered instrument for assessing alcohol craving (Flannery et al-1999). Frequency, intensity, and duration of thoughts about drinking are assessed along with ability to resist drinking. Each item is a Likert scale ranging from 0 to 6. The items are summed to produce a total score ranging from 0 to 30. Higher total scores are indicative of greater craving.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18.0" spread="4.5"/>
                    <measurement group_id="B2" value="17.7" spread="3.8"/>
                    <measurement group_id="B3" value="17.8" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Current smoker (past week)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cue-elicited Craving</title>
        <description>The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome).</description>
        <time_frame>Study Week 3</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
          </group>
        </group_list>
        <measure>
          <title>Cue-elicited Craving</title>
          <description>The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome).</description>
          <population>mITT</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="0.4"/>
                    <measurement group_id="O2" value="2.2" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Heavy Drinking Days</title>
        <description>The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males.</description>
        <time_frame>Weeks 3-6</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Heavy Drinking Days</title>
          <description>The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males.</description>
          <population>mITT</population>
          <units>percentage of heavy drinking days</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.7" spread="4.9"/>
                    <measurement group_id="O2" value="21.0" spread="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6).</title>
        <description>The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6).</description>
        <time_frame>Weeks 3-6</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6).</title>
          <description>The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6).</description>
          <population>mITT</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cigarettes Smoked Per Week</title>
        <description>The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis.</description>
        <time_frame>Weeks 3-6</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline - Smokers at Baseline</title>
            <description>Subjects randomized to varenicline who smoked at baseline</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Smokers at Baseline</title>
            <description>Subjects randomized to placebo who smoked at baseline</description>
          </group>
        </group_list>
        <measure>
          <title>Cigarettes Smoked Per Week</title>
          <description>The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis.</description>
          <population>mITT</population>
          <units>cigarettes per week</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" spread="7.7"/>
                    <measurement group_id="O2" value="64.0" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Penn Alcohol Craving Scale</title>
        <description>Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6.</description>
        <time_frame>Study Weeks 3, 4, 5, 6 (assessed weekly during this period)</time_frame>
        <population>mITT</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
          </group>
        </group_list>
        <measure>
          <title>Penn Alcohol Craving Scale</title>
          <description>Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6.</description>
          <population>mITT</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8" spread="1.1"/>
                    <measurement group_id="O2" value="10.9" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Weeks 1 to 6</time_frame>
      <desc>Definitions and descriptions are consistent with those in clinicaltrials.gov.</desc>
      <group_list>
        <group group_id="E1">
          <title>Varenicline</title>
          <description>1 mg BID (2 capsules BID)&#xD;
Varenicline: 1 mg BID</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>1 mg BID (2 capsules BID)&#xD;
Placebo oral capsule: 1 mg BID</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal Dreams</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Bright Urine</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Gynecological bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Health Scientist Administrator</name_or_title>
      <organization>National Institute on Alcohol Abuse and Alcoholism</organization>
      <phone>301-443-0788</phone>
      <email>falkde@mail.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03035708
org study id: HLAB 001
nct id: NCT03035708
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study
      designed to assess the effects of varenicline as compared with placebo on responses to in
      vivo alcohol cue exposure in the human laboratory setting.
This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study
      designed to assess the effects of varenicline as compared with placebo on responses to in
      vivo alcohol cue exposure in the human laboratory setting. After signing informed consent,
      subjects will be screened for eligibility including medical history, physical examination,
      vital signs, electrocardiogram (ECG), drinking history by the timeline follow-back (TLFB)
      method, alcohol breathalyzer test, Clinical Institute Withdrawal Assessment for
      Alcohol-revised (CIWA), medication use, MINI neuropsychiatric interview, urine toxicology
      screen, clinical chemistry, response to cue reactivity, and Columbia Suicide Severity Rating
      Scale (CSSR-S). Women of child-bearting potential will have a pregnancy test. If eligible for
      the study, subjects will be randomized using a stratified permuted block randomization
      procedure in an approximate 1:1 ratio (targeting 24 subjects per group - 12 subjects per
      group per site) to receive either varenicline or placebo for 6 weeks. Any nicotine use versus
      no use (cigarettes, cigars, chewing tobacco, electronic cigarettes, etc.) in the week before
      randomization is the stratification variable.

      Varenicline or matched placebo will be titrated over the first week of the study up the
      maintenance dose of 1 mg (active) or two capsules (placebo) taken orally BID for an
      additional 5 weeks. Subjects will be seen in the clinic at screening, at randomization and 6
      other times during the study. A final follow-up telephone interview will occur during Week 9
      (2 weeks after the end of study visit).

      After the first two weeks and after five weeks of investigational product administration at
      Study Week 3 and Study Week 6, respectively, subjects will undergo a cue reactivity paradigm
      session (HLAB) including 4 individual visual analog scale (VAS) items assessing alcohol
      craving, 2 VAS items assessing emotional reactivity to picture stimuli, and 2 items assessing
      emotional manipulation. Immediately after the HLAB session, subjects will view each picture
      again and record the emotion felt using the Self-Manikin Assessment (SAM).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Cue-elicited Craving
time frame: Study Week 3
description: The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome).
measure: Percent Heavy Drinking Days
time frame: Weeks 3-6
description: The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males.
measure: The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6).
time frame: Weeks 3-6
description: The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6).
measure: Cigarettes Smoked Per Week
time frame: Weeks 3-6
description: The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis.
measure: Penn Alcohol Craving Scale
time frame: Study Weeks 3, 4, 5, 6 (assessed weekly during this period)
description: Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6.
arm group label: varenicline
arm group type: Experimental
description: 1 mg BID (2 capsules BID)
arm group label: Placebo
arm group type: Placebo Comparator
description: 1 mg BID (2 capsules BID)
intervention type: Drug
intervention name: Varenicline
description: 1 mg BID
arm group label: varenicline
other name: Chantix
intervention type: Drug
intervention name: Placebo oral capsule
description: 1 mg BID
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Raye Litten, PhD
role: Study Director
affiliation: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Alcohol Drinking
mesh term: Varenicline
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 