Clinical trial NCT00695500
Conditions: Alcohol Drinking
Keywords: Varenicline Alcohol Alcohol Use
Sponsor: Vijay Ramchandani, Ph.D.
Start date: 2008-06-01; Completion date: 2015-06-01
Enrollment: 50 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will determine whether varenicline, a drug that acts on the brain's nicotine receptors and is used to help smokers stop smoking, will have an impact on alcohol self-administration.

People between 24 and 60 years of age who regularly consume alcoholic drinks (more than 15 drinks per week for women, and more than 20 drinks per week for men) may be eligible for this study. The study requires five outpatient visits and one overnight hospital admission at the NIH Clinical Center.

Participants undergo the following procedures:

Visit 1 (outpatient: 4-5 hours)

* Standard assessments, including vital signs measurements, breathalyzer test, blood and urine tests (including pregnancy test for females), questionnaires about mood, symptoms, alcohol use and smoking, if applicable
* Questionnaires about medical and psychological status
* Health assessment and assessment of alcohol drinking behavior

Visit 2 (outpatient: 8 hours)

* Standard assessments (see above)
* Computer-Assisted Self-infusion of Ethanol (CASE) session: Subjects will receive a priming intravenous infusion of alcohol. After 25 min, they will be allowed to give themselves additional exposures of alcohol over a period of 2 hours by pressing a button on a computer that controls the infusion pump.

Visit 3 (outpatient: 2 hours)

-Standard assessments

Visit 4 (outpatient: 8 hours)

* Standard assessments
* Brain functional magnetic resonance imaging scan (MRI). This test uses a magnetic field and radio waves to produce images of the brain. The patient lies on a table that can slide in and out of the scanner, wearing earplugs to muffle loud sounds that occur during the scanning process. Initial pictures are taken of the brain's structure and additional scans measure brain activity while the subject performs simple tasks.
* Alcohol Infusion. Subjects receive an intravenous infusion of alcohol while in the MRI scanner to measure the brain s response to alcohol.

Visit 5 (overnight)

* Standard assessments
* Repeat CASE session
* Interview about the subject's experiences participating in the protocol, including any symptoms and urges to drink

Visit 6 (outpatient)

* Standard assessments (without blood tests)
* Interview about participation in the study

Telephone follow-up

After 3 weeks, subjects are called to check on their symptoms and gather information on their drinking and, if applicable, smoking.

Detailed description:
Objective:

Considerable clinical and experimental evidence in humans and animal models links nicotine use with heavy alcohol consumption. Varenicline, an alpha4beta2 (nicotinic) acetylcholine receptor (nAchR) partial agonist, is an oral medication approved by the FDA (2006) for smoking cessation. Recently, it has been shown to reduce alcohol consumption in a rodent model of alcohol dependence. In the present short-term experimental study, it will be assessed primarily for its ability to reduce alcohol self-administration in heavy drinkers. Secondarily, its effects on alcohol urges (cravings), as well as smoking parameters will be measured. In addition, effects of varenicline on incentive motivation for alcohol and the underlying brain reward system activation, as well as on activation of brain reward systems in response to intravenously administered alcohol will be measured.

Study Population:

Fifty healthy, adults (smokers and non-smokers), age 21 to 60 years, will be studied. Individuals must drink alcohol regularly at a heavy level, on average greater than 20 drinks per week for men, and greater than 15 drinks per week for women, and not be seeking help for alcohol-related problems.

Design:

Following protocol screening and medical evaluation, qualified subjects will undergo an initial ( pre-study drug ) intravenous alcohol self-administration session (hereafter, called computer-assisted self-infusion of ethanol, or CASE). Following this, subjects will be randomized to varenicline or placebo. Subjects will be clinically evaluated on three occasions while on study drug: once after one week of study medication; again, prior to the fMRI; and again, at the end of treatment, when they undergo the second ( on-study drug ) CASE session. Between days 13 and 21, all subjects will be scheduled to undergo functional magnetic resonance imaging (fMRI) of the brain while performing a task designed to evaluate the incentive salience for alcohol cues as well as the pharmacological effects of alcohol. Thereafter, all subjects will receive two courses of counseling for heavy drinking, using motivational enhancement techniques, aimed at enhancing their readiness for behavioral change and seeking treatment, if needed.

Outcome Measures:

The primary outcome will be the peak breath alcohol exposure achieved during the on-study drug CASE session. Secondary outcomes during the study drug phase will include measures of alcohol consumption, and urges to drink, as well as alcohol cravings and effects during the on-study drug CASE session. Additionally, fMRI BOLD responses in the ventral striatum, an area involved in brain reward circuitry and shown to be activated by acute IV alcohol administration as well as anticipation of working for reward will be measured. In smokers, cigarette use and quite rates as well as urges to smoke and nicotine withdrawal will also be measured. Safety and tolerability will be followed during the course of taking study drug with symptom checklists, profiles of mood and anxiety and by clinical interview. Serum varenicline concentrations will also be measured to assess compliance and control for potential pharmacokinetic variation.

Arms: arm 1: Varenicline tablets, 2 mg per day for 3 weeks arm 2: Placebo tablets, 0 mg per day for 3 weeks
Interventions: intervention 1: Varenicline intervention 2: Placebo
Intervention descriptions: intervention 1: Varenicline tablets, 2 mg per day for 3 weeks intervention 2: Placebo tablets, 0 mg per day for 3 weeks

Protocol documents: