Human Laboratory Study of Varenicline for Alcohol Use Disorder

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).

Inclusion criteria

To be eligible, the subject must:

• Be at least 21 years of age.
• Meet the DSM 5 criteria for alcohol use disorder of a least moderate severity (AUD-MS).
• Be seeking treatment for AUD and desire a reduction or cessation of drinking.
• Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol.
• Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal:

• oral contraceptives,
• contraceptive sponge,
• patch,
• double barrier (diaphragm/spermicidal or condom/spermicidal),
• intrauterine contraceptive system,
• levonorgestrel implant,
• medroxyprogesterone acetate contraceptive injection,
• complete abstinence from sexual intercourse, and/or
• hormonal vaginal contraceptive ring.
• Be able to take oral medication and be willing to adhere to the medication regimen.
• Complete all assessments required at screening and baseline.
• Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing in the next 2 months.
• Not anticipate any significant problems with transportation arrangements or available time to travel to the study site over the next 2 months.
• Not have any unresolved legal problems that could jeopardize continuation or completion of the study.
• And others.

Exclusion criteria

• Contact site for additional information