A Novel Human Lab Model for Screening AUD Medications
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Intervention: Placebo; Naltrexone; Varenicline
Intervention description: Matched to active medication; 50 mg once a day; 1 mg twice a day
Intervention MeSH terms: Naltrexone; Varenicline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, placebo-controlled, 3-arm, parallel-group study of naltrexone (50 mg QD) and varenicline (1 mg BID).
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: The study team, medical personnel, and participants will be blind to drug condition.
Enrollment: 53.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alcohol Use Disorder; Medications Development

Summary:

      This study design consists of a randomized, double-blind, placebo-controlled, 3-arm,
      parallel-group study of naltrexone (50 mg QD) and varenicline (1 mg BID). A total of 108 men
      and women with current AUD (moderate or severe) and reporting intrinsic motivation to change
      their drinking, will be randomly assigned to receive naltrexone (50 mg QD), varenicline (1 mg
      BID) or matched placebo. Post-randomization, all participants will complete an alcohol
      cue-reactivity paradigm prior to the initial dose of study medication. After a week-long
      medication titration period, participants will be asked to complete a 7-day practice quit
      attempt, during which they will have daily virtual visits (phone and online) where they will
      report on their alcohol use. Additionally, a second cue-reactivity paradigm will be conducted
      90 minutes following study drug administration on final day of the practice quit attempt (Day
      14).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be between the ages of 21 and 65

          2. Meet current (i.e., past 12-month) DSM-5 diagnostic criteria for AUD moderate or
             severe

          3. Have intrinsic motivation to reduce or quit drinking (defined as self-reported
             intention to reduce or quit drinking within the next 6 months)

          4. Report drinking at least 28 drinks per week if male (14 drinks per week if female) in
             the 28 days prior to the initial consent

          5. Have reliable internet access

        Exclusion Criteria:

          1. Have a current (last 12 months) DSM-5 diagnosis of substance use disorder for any
             psychoactive substances other than alcohol and nicotine

          2. Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic
             disorder

          3. Have a positive urine screen for drugs other than cannabis

          4. Have clinically significant alcohol withdrawal symptoms as indicated by a score ≥ 10
             on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R)

          5. Have an intense fear of needles or have had any adverse reactions to needle puncture

          6. Be pregnant, nursing, or planning to become pregnant while taking part in the study;
             and must agree to one of the following methods of birth control (if female), unless
             she or partner are surgically sterile:

               -  Oral contraceptives

               -  Contraceptive sponge

               -  Patch

               -  Double barrier

               -  Intrauterine contraceptive device

               -  Etonogestrel implant

               -  Medroxyprogesterone acetate contraceptive injection

               -  Complete abstinence from sexual intercourse

               -  Hormonal vaginal contraceptive ring

          7. Have a medical condition that may interfere with safe study participation (e.g.,
             unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)

          8. Be currently taking any psychotropic medications that, in the opinion of the
             investigators, compromises participant safety

          9. Be currently taking or have had previous experience with either naltrexone or
             varenicline

         10. Have any other circumstances that, in the opinion of the investigators, compromises
             participant safety