A Novel Human Lab Model for Screening AUD Medications
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Study type: Interventional
Phase: Phase 2

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).
    

Detailed description: 
      Recruitment: Participants will be recruited from the community through online and newspaper
      advertisements. Campaigns in local buses and print publications (e.g., LA Weekly) will also
      be implemented. Targeted recruitment will also take place through a lab database of previous
      study participants who agreed to be contacted for future studies.

      Telephone Screen: Individuals who call the lab (in response to flyers and advertisements)
      expressing interest in the study will receive detailed information about the study
      procedures, and if they remain interested they will complete a telephone screen performed by
      a trained research assistant for self-reported inclusion and exclusion criteria. Those who
      appear eligible will be invited to the laboratory for an initial in-person screening session.

      Initial Screening: Prior to conducting any research related procedures, research staff will
      conduct the informed consent process, which details the procedures to take place during the
      screening visit. Informed consent will be a three-part process. First, participants will be
      asked to read and provide verbal consent for breathalyzer. If the breathalyzer is above
      0.000, the visit will be stopped and the participant will not be compensated. The participant
      will be given an opportunity to reschedule the visit for another day. If the breathalyzer
      test is negative, the written informed consent form will be reviewed and signed by the
      participant and study staff outlining procedures for the initial screening visit. A second
      written consent form will be reviewed and signed in the presence of the study physician at
      the medical screening visit if the participant is found eligible to continue to that visit.
      At the initial screening visit, subjects will be asked to provide a urine sample to test for
      drugs of abuse and pregnancy (if female), and will complete a series of questionnaires and
      interviews (described in detail below) to determine initial eligibility. This visit will take
      approximately 1 hour. Following the initial in-person screening, the study coordinator will
      meet with the PI to determine if the participant is eligible to continue to the medical
      screening based on study inclusion/exclusion criteria.

      Medical Screening: Those participants who appear to be eligible after the initial screening
      visit, will then be scheduled for a second screening visit. This visit will be conducted by
      the study physician and will start with a breathalyzer test. If the breathalyzer is above
      0.000, the visit will be stopped and the participant will not be compensated. The participant
      will be given an opportunity to reschedule the visit for another day. If the breathalyzer
      test is negative, the physician will conduct the second written (experimental) consent;
      medical history interview and physical exam. In addition, a urine sample will be obtained for
      repeat drug screen and pregnancy tests. The participant will then be accompanied by research
      personnel to the CTRC for blood specimen collection including Comprehensive Metabolic Panel
      and Complete Blood Count to evaluate overall health; and EKG to screen for medical conditions
      that could make study participation medically unsafe. The study physician will review each
      participant's medical history, vital signs, weight, review of systems, and laboratory tests,
      including liver function tests (LFTs), drug screen, chemistry screen, and urine pregnancy
      screen to determine if it is medically safe for the participant to take the study medication.
      Any subject who is excluded from the study will be compensated for their time in the
      screening session and will be offered referrals for alcohol treatment in the community.

      Randomization and Medication Titration: Participants who are eligible after the physical exam
      will be randomized to one of three treatment conditions (VAR, NTX, or PLA). Urn randomization
      will be used to balance the groups by gender, smoking status (as reported on question 1 of
      the Fagerstrom Test for Nicotine Dependence), and drinking status ('heavy' drinker defined as
      28 or more drinks per week for males/14 or more drinks per week for females, or 'very heavy'
      drinker, defined as 35 or more drinks per week for males/28 or more drinks per week for
      females). The UCLA Research Pharmacy will manage the blind. The three treatment conditions
      will not be different in appearance or method of administration. All participants will
      undergo a week-long medication titration period prior to the onset of the practice quit
      attempt.

      Practice-Quit Attempt: During the practice-quit attempt, participants will be instructed to
      abstain completely from drinking alcohol during a 7-day practice quit period. This period
      will begin on Day 8 of study medication dosing. During this period, participants will
      complete daily virtual visits to report on their drinking, mood and craving for alcohol
      during the previous day in a daily diary assessment (DDA).

      Study Medication: On Day 1, participants will report to the laboratory to complete the
      alcohol cue-reactivity paradigm and receive their first medication dose under direct
      observation of study staff. They will receive a 7-day supply of study medication in blister
      packs with AM and PM dosing clearly distinguished for the titration procedure. After reaching
      full medication dose at the end of one week, participants will come to the laboratory on Day
      8 to begin the practice quit attempt and to take AM dose of study medication daily in the lab
      under direct observation of study staff. Additionally, on the first day of the practice-quit
      attempt (Day 8), participants will receive a second 7-day supply of study medication. All
      study medication will be prepared by the UCLA Research Pharmacy and will be identically
      matched in appearance (opaque capsules with 50 mg of riboflavin to aid in medication
      compliance procedures) and the medication labels will not reveal the drug identity.

      Alcohol Cue Reactivity Sessions (CR): Randomized participants will complete a cue-exposure
      paradigm at two time points during the study, once on Day 1 prior to ingesting the first dose
      of study medication, and again on Day 14, approximately 90 minutes after study drug
      administration. Alcohol cue exposure will follow well-established experimental procedures.
      Sessions will begin with a 3-minute relaxation period. Participants will then hold and smell
      a glass of water for 3 minutes to control for the effects of simple exposure to any potable
      liquid. Next, participants will hold and smell a glass of their preferred alcoholic beverage
      for 3 minutes. Order is not counterbalanced because of carryover effects that are known to
      occur. Participants (who are smokers) will be allowed a smoke break immediately prior to the
      CR assessment. After every 3 minutes of exposure, participants will rate their urge to drink
      on the Alcohol Urge Questionnaire (AUQ) and their mood on the Profile of Mood States (POMS).
      AUQ score (alcohol minus water) is the primary outcome for the CR.

      Brief Counseling Session: All participants will meet with a trained study counselor briefly
      after the second cue exposure session on Day 14 to discuss their responses to the alcohol
      cues and discuss local treatment options. The counselor will begin by introducing him/herself
      and thanking the participant for his/her participation. He/she will continue by providing the
      participant with feedback on their responses on various individual difference measures
      (drinking patterns, severity of AUD diagnosis, family history, CIWA, depression, and other
      drug use). The counselor will probe for participants' attitudes towards these responses and
      diagnoses, and provide both informational and emotional support. Next, the counselor will go
      over the participant's history of alcohol treatment, in order to identify potential barriers
      to treatment access. He/she will discuss local treatment options with the participant,
      including the participant's primary care provider, self-help groups, and the UCLA Psychology
      Clinic. Lastly, the counselor will go over the "Rethinking Drinking" pamphlet with the
      participant, pointing out specific treatment options discussed in the session, and will
      address any questions or concerns.
    

Intervention name(s): Placebo; Naltrexone; Varenicline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Matched to active medication; 50 mg once a day; 1 mg twice a day
Other intervention name(s): PLAC; NTX; VAR; Chantix
Intervention MeSH terms: Naltrexone; Varenicline
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)
Primary purpose: Treatment
Keywords: Alcohol Use Disorder; Medications Development