<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/NCT02193256</url>
  </required_header>
  <id_info>
    <org_study_id>1402013410</org_study_id>
    <secondary_id>K05AA014715</secondary_id>
    <nct_id>NCT02193256</nct_id>
  </id_info>
  <brief_title>Varenicline + Prazosin for Heavy Drinking Smokers</brief_title>
  <official_title>Pilot Trial of Varenicline and Prazosin to Treat Heavy Drinking Smokers</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine the effect of varenicline and prazosin on smoking,&#xD;
      drinking, and sleep among cigarette smokers who report heavy alcohol use. Varenicline is an&#xD;
      FDA approved smoking cessation medication. Some smokers report sleep problems when taking&#xD;
      varenicline. This study will test whether using prazosin, which is an FDA-approved blood&#xD;
      pressure medication, in combination with varenicline reduces sleep problems that can be&#xD;
      associated with using varenicline for smoking cessation. In addition, the study will examine&#xD;
      the combined effects of these medications on smoking and drinking.&#xD;
&#xD;
      Hypothesis: Varenicline plus prazosin will result in lower rates of vivid dreams and insomnia&#xD;
      symptoms/sleep discontinuity than varenicline alone prior to the 3-day practice quit attempt.&#xD;
&#xD;
      Hypothesis: Varenicline plus prazosin will result in lower rates of vivid dreams and insomnia&#xD;
      symptoms/sleep discontinuity than varenicline alone during the 3-day practice quit attempt.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study comprises an 8-week double-blind, within-subjects, crossover design of varenicline&#xD;
      (up to 2mg per day) plus either prazosin (up to 8mg per day) (V+P) or placebo (V) with 20&#xD;
      heavy drinking smokers. Each medication phase is 3 weeks with a 2-week medication washout in&#xD;
      between. Participants are asked to make a practice quit attempt for 3 days the last week of&#xD;
      each medication phase.&#xD;
&#xD;
      This is an exploratory study to look at two primary aims:&#xD;
&#xD;
        1. Evaluate the effect of prazosin on sleep disturbance caused by varenicline in heavy&#xD;
           drinking smokers prior to quitting smoking.&#xD;
&#xD;
           Hypothesis: V+P will result in lower rates of vivid dreams and insomnia symptoms/sleep&#xD;
           discontinuity than V alone.&#xD;
&#xD;
        2. Evaluate the effect of prazosin on sleep disturbance caused by varenicline during&#xD;
           smoking cessation in heavy drinking smokers.&#xD;
&#xD;
      Hypothesis: V+P will result in lower rates of vivid dreams and insomnia symptoms/sleep&#xD;
      discontinuity than V alone We will also investigate the combined effects of prazosin and&#xD;
      varenicline on smoking behavior (i.e., smoking urge) and alcohol consumption (i.e., drinks&#xD;
      per drinking day) as exploratory aims.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of prazosin on sleep disturbance caused by varenicline prior to quitting smoking</measure>
    <time_frame>Two weeks</time_frame>
    <description>Sleep disturbance will be measured using self-report questionnaires (Insomnia Severity Index, Pittsburgh Sleep Quality Index, Pittsburgh Sleep Diary, Dream Quality Questionnaire) and objective sleep-monitoring devices.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of prazosin on sleep disturbance caused by varenicline during smoking cessation</measure>
    <time_frame>One week</time_frame>
    <description>Sleep disturbance will be measured using self-report questionnaires (Insomnia Severity Index, Pittsburgh Sleep Quality Index, Pittsburgh Sleep Diary, Dream Quality Questionnaire) and objective sleep-monitoring devices.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Number of cigarettes smoked</measure>
    <time_frame>Three weeks</time_frame>
    <description>The investigators will compare the combined effects of prazosin and varenicline on the number of cigarettes smoked with varenicline alone.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of drinks per drinking day</measure>
    <time_frame>Three weeks</time_frame>
    <description>The investigators will compare the combined effects of prazosin and varenicline on alcohol consumption (i.e., number of drinks per drinking day) with varenicline alone as an exploratory aim.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Cigarette Smoking</condition>
  <condition>Alcohol Use Disorders</condition>
  <arm_group>
    <arm_group_label>Varenicline plus Prazosin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Varenicline: .5mg for 3 days then 1mg daily for 4 days (Week 1) then 2mg daily thereafter (Weeks 2-3). Prazosin: 1mg for 3 days, then 3mg for 4 days (Week 1), (2) 6mg for 3 days, then 8mg for 4 days (Week 2), and (3) 8mg (Week 3).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Varenicline plus Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Varenicline: .5mg for 3 days then 1mg daily for 4 days (Week 1) then 2mg daily thereafter (Weeks 2-3). Placebo: placebo will be given instead of prazosin (Weeks 1-3)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline</intervention_name>
    <description>Titrated over 1 week to a maximum dose of 2mg/day</description>
    <arm_group_label>Varenicline plus Placebo</arm_group_label>
    <arm_group_label>Varenicline plus Prazosin</arm_group_label>
    <other_name>Chantix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prazosin</intervention_name>
    <description>Titrated over 3 weeks to a maximum dose of 8mg/day</description>
    <arm_group_label>Varenicline plus Prazosin</arm_group_label>
    <other_name>Minipress</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Varenicline plus Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. at least 18 years of age;&#xD;
&#xD;
          2. current smoker [quantity of ≥ cigarettes per smoking day, frequency of ≥3 times per&#xD;
             week, and urinary cotinine ≥2 on NicAlert dipstick;&#xD;
&#xD;
          3. at least 4 occasions of heavy drinking in the past 30 days [5 or 4 standard drinks per&#xD;
             occasion for males and females, respectively];&#xD;
&#xD;
          4. no history of severe alcohol withdrawal syndrome;&#xD;
&#xD;
          5. no new onset of psychiatric illness or psychotropic medications in last 90 days;&#xD;
&#xD;
          6. no severe psychiatric illness [schizophrenia, bipolar disorder] or PTSD;&#xD;
&#xD;
          7. no substance dependence other than nicotine, alcohol or marijuana;&#xD;
&#xD;
          8. no medical contraindications for varenicline or prazosin;&#xD;
&#xD;
          9. are willing to take medication and wear portable sleep monitoring devices;&#xD;
&#xD;
         10. no risk for sleep apnea syndrome;&#xD;
&#xD;
         11. able to read and write in English;&#xD;
&#xD;
         12. not interested in quitting smoking immediately.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. unable to complete the informed consent;&#xD;
&#xD;
          2. do not meet criteria for heavy drinking;&#xD;
&#xD;
          3. do not meet criteria for current smokers;&#xD;
&#xD;
          4. unable to read/understand English;&#xD;
&#xD;
          5. exhibit serious psychiatric illness (i.e. schizophrenia, bipolar disorder, severe&#xD;
             major depression, panic disorder, borderline personality disorder), organic mood or&#xD;
             mental disorders by history of psychological examination;&#xD;
&#xD;
          6. meet criteria for alcohol dependence in past 12 months that is clinically severe;&#xD;
&#xD;
          7. meet criteria for drug dependence in the last 12 months aside from marijuana, nicotine&#xD;
             and alcohol;&#xD;
&#xD;
          8. are seeking to quit smoking immediately;&#xD;
&#xD;
          9. report current psychosis or suicidality;&#xD;
&#xD;
         10. are a female of childbearing potential who is pregnant, nursing, or not practicing&#xD;
             effective contraception (oral, injectable, or implantable contraceptives, intrauterine&#xD;
             device, or barrier method with spermicide);&#xD;
&#xD;
         11. exhibit current, clinically significant physical disease or abnormality based on&#xD;
             medical history, physical examination, or routine laboratory evaluation including:&#xD;
&#xD;
               1. any unexplained elevations in liver enzymes (i.e. transaminases, bilirubin);&#xD;
&#xD;
               2. clinically significant, unstable cardiovascular disease/uncontrolled&#xD;
                  hypertension;&#xD;
&#xD;
               3. hepatic or renal impairment;&#xD;
&#xD;
               4. severe obstructive pulmonary disease;&#xD;
&#xD;
               5. diabetes mellitus requiring insulin or certain oral medications (i.e.&#xD;
                  sulfonylureas) and an A1C hemoglobin test score of &gt;7 for participants not&#xD;
                  prescribed these medications;&#xD;
&#xD;
               6. baseline systolic blood pressure higher than 150 mm Hg of diastolic blood&#xD;
                  pressure higher than 95 mm Hg; (g) are scheduled for cataract surgery; (h) have a&#xD;
                  diagnosis of narcolepsy;&#xD;
&#xD;
         12. have a history of cancer (except treated basal cell or squamous cell carcinoma of the&#xD;
             skin)&#xD;
&#xD;
         13. have a history of clinically significant allergic reactions;&#xD;
&#xD;
         14. have used any psychotropic drug in the past month, except individuals who are on a&#xD;
             stable dose of a Selective Serotonin Reuptake Inhibitor for at least two months;&#xD;
&#xD;
         15. intend to donate blood or blood products during the treatment phase of the study;&#xD;
&#xD;
         16. have a Body Mass Index (calculated as weight in kilograms divided by the square of&#xD;
             height in meters) less than 15 or greater than 28 or weight less than 45 kg.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisa M Fucito, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>March 10, 2020</last_update_submitted>
  <last_update_submitted_qc>March 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>varenicline</keyword>
  <keyword>prazosin</keyword>
  <keyword>cigarette smoking</keyword>
  <keyword>alcohol drinking</keyword>
  <keyword>sleep</keyword>
  <keyword>dreams</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prazosin</mesh_term>
    <mesh_term>Varenicline</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02193256
org study id: 1402013410
secondary id: K05AA014715
nct id: NCT02193256
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to examine the effect of varenicline and prazosin on smoking,
      drinking, and sleep among cigarette smokers who report heavy alcohol use. Varenicline is an
      FDA approved smoking cessation medication. Some smokers report sleep problems when taking
      varenicline. This study will test whether using prazosin, which is an FDA-approved blood
      pressure medication, in combination with varenicline reduces sleep problems that can be
      associated with using varenicline for smoking cessation. In addition, the study will examine
      the combined effects of these medications on smoking and drinking.

      Hypothesis: Varenicline plus prazosin will result in lower rates of vivid dreams and insomnia
      symptoms/sleep discontinuity than varenicline alone prior to the 3-day practice quit attempt.

      Hypothesis: Varenicline plus prazosin will result in lower rates of vivid dreams and insomnia
      symptoms/sleep discontinuity than varenicline alone during the 3-day practice quit attempt.
The study comprises an 8-week double-blind, within-subjects, crossover design of varenicline
      (up to 2mg per day) plus either prazosin (up to 8mg per day) (V+P) or placebo (V) with 20
      heavy drinking smokers. Each medication phase is 3 weeks with a 2-week medication washout in
      between. Participants are asked to make a practice quit attempt for 3 days the last week of
      each medication phase.

      This is an exploratory study to look at two primary aims:

        1. Evaluate the effect of prazosin on sleep disturbance caused by varenicline in heavy
           drinking smokers prior to quitting smoking.

           Hypothesis: V+P will result in lower rates of vivid dreams and insomnia symptoms/sleep
           discontinuity than V alone.

        2. Evaluate the effect of prazosin on sleep disturbance caused by varenicline during
           smoking cessation in heavy drinking smokers.

      Hypothesis: V+P will result in lower rates of vivid dreams and insomnia symptoms/sleep
      discontinuity than V alone We will also investigate the combined effects of prazosin and
      varenicline on smoking behavior (i.e., smoking urge) and alcohol consumption (i.e., drinks
      per drinking day) as exploratory aims.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Effect of prazosin on sleep disturbance caused by varenicline prior to quitting smoking
time frame: Two weeks
description: Sleep disturbance will be measured using self-report questionnaires (Insomnia Severity Index, Pittsburgh Sleep Quality Index, Pittsburgh Sleep Diary, Dream Quality Questionnaire) and objective sleep-monitoring devices.
measure: Effect of prazosin on sleep disturbance caused by varenicline during smoking cessation
time frame: One week
description: Sleep disturbance will be measured using self-report questionnaires (Insomnia Severity Index, Pittsburgh Sleep Quality Index, Pittsburgh Sleep Diary, Dream Quality Questionnaire) and objective sleep-monitoring devices.
measure: Number of cigarettes smoked
time frame: Three weeks
description: The investigators will compare the combined effects of prazosin and varenicline on the number of cigarettes smoked with varenicline alone.
measure: Number of drinks per drinking day
time frame: Three weeks
description: The investigators will compare the combined effects of prazosin and varenicline on alcohol consumption (i.e., number of drinks per drinking day) with varenicline alone as an exploratory aim.
arm group label: Varenicline plus Prazosin
arm group type: Active Comparator
description: Varenicline: .5mg for 3 days then 1mg daily for 4 days (Week 1) then 2mg daily thereafter (Weeks 2-3). Prazosin: 1mg for 3 days, then 3mg for 4 days (Week 1), (2) 6mg for 3 days, then 8mg for 4 days (Week 2), and (3) 8mg (Week 3).
arm group label: Varenicline plus Placebo
arm group type: Placebo Comparator
description: Varenicline: .5mg for 3 days then 1mg daily for 4 days (Week 1) then 2mg daily thereafter (Weeks 2-3). Placebo: placebo will be given instead of prazosin (Weeks 1-3)
intervention type: Drug
intervention name: Varenicline
description: Titrated over 1 week to a maximum dose of 2mg/day
arm group label: Varenicline plus Placebo
arm group label: Varenicline plus Prazosin
other name: Chantix
intervention type: Drug
intervention name: Prazosin
description: Titrated over 3 weeks to a maximum dose of 8mg/day
arm group label: Varenicline plus Prazosin
other name: Minipress
intervention type: Drug
intervention name: Placebo
arm group label: Varenicline plus Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lisa M Fucito, PhD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Prazosin
mesh term: Varenicline