Varenicline (Chantix™) for the Treatment of Alcohol Dependence

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of varenicline (Chantix™) for the treatment of alcohol dependence.

Detailed Description
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By both providing a low level of reinforcement and down-grading any high associated with concurrent administration of the abused drug, combined agonist/antagonist therapies promote both initial and sustained abstinence. Based on varenicline's specific affinity for the nicotinic acetylcholine receptors that are implicated in alcohol reward circuitry, it appears to be a good candidate for treatment of alcohol dependence. Alcohol can exert its reinforcing and dopamine-enhancing effects through activation of nicotinic receptors. In addition to its partial agonist activity at heteromeric α4β2 nicotinic acetylcholine receptors, varenicline has also been shown to be a full agonist at homomeric α7 nicotinic acetylcholine receptors. That full agonism at α7 may be key in reducing alcohol withdrawal and craving during early alcohol abstinence, and thus reducing relapse, as α7 receptors are implicated in the neural reward circuitry activated by alcohol use.

Official Title
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A Phase II, Randomized, Double-Blind Pilot Trial of Varenicline (Chantix™) for the Treatment of Alcohol Dependence

Conditions
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Alcoholism

Intervention / Treatment
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* Drug: varenicline
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Males and females, 18-70 years old. 2. Meets DSM-IV criteria for current diagnoses of alcohol dependence, determined by the SCID-IV (First, 1996). 3. Meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell, 1995) drank within 30 days of intake day, reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i.e., a minimum of 40% days drinking), and has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period. 4. Three consecutive days of abstinence from alcohol, determined by self-reports and confirmed by a negative breathalyzer tests immediately before the day of randomization, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight on the day of randomization. 5. Lives a commutable distance from the TRC and agrees to attend all research visits including follow-up visits. Speaks, understands, and prints in English. Exclusion Criteria: Has evidence of dependence on a substance other than alcohol (except nicotine or marijuana); or tests positive on the urine drug screen and on a single allowed retest, during the screening week, with the exception of a THC positive urine, and/or a).positive result for benzodiazepines prescribed by a doctor for medically indicated detox (prescription required). Has hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 4.5 times normal after the required 3 days of abstinence, or elevated bilirubin (>1.3) (one retest allowed at the discretion of the Medical Director). Meets diagnostic criteria for a current unstable or serious psychiatric or medical illness. For example, bipolar affective disorder, schizophrenia or any other psychotic disorder, or organic mental disorder; has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis, regional enteritis, or gastrointestinal bleeding) disease. Has taken any psychotropic medications (including disulfiram, naltrexone or acamprosate) regularly within the last 2 weeks or needs immediate treatment with a psychotropic medication (with the exception of detoxification medications or benadryl used sparingly for sleep). Tests positive on a pregnancy test, is contemplating pregnancy in the next 12 months, is nursing, or is not using an effective contraceptive method if the subject is of child-bearing potential. Has participated in any investigational drug trial within 30 days prior to the study. Subjects mandated to treatment based upon a legal decision or as a condition of employment. This will be assessed by the subject's self-report. Known hypersensitivity to varenicline. Subjects with known AIDS or other serious illnesses that may require hospitalization during the study. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator. (ECG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: varenicline<br>* 1.0 mg BID for 12 weeks<br>* Other names: Chantix;|
| Placebo Comparator: 2<br> | Drug: placebo<br>* BID 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Heavy Drinking Days Per Week. | Rate of heavy drinking days per week (defined as five drinks per day for men, four drinks per day for women) as determined by self-report on the time-line follow-back (TLFB). | 12 weeks of treatment and one month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Addiction Severity Index (ASI) Alcohol Composite Score at End of Study. | The Addiction Severity Index (ASI) is a semistructured interview that measures the severity of addiction in 25 questions concerning seven problem areas: medical problems, employment problems, drug use, alcohol use, family and social problems, criminality, and psychiatric problems. Each problem area is measured as its own Compsite Score. Each Composite Score total ranges between 0 (no endorsement of any problems) and 1 (maximal endorsement of all problems). Higher scores (i.e., those closer to 1) on each Composite Score indicate more difficulty/lower functioning in that area, while lower scores (i.e., those closer to 0) indicate higher functioning/less difficulty in that area. As such, the Addiction Severity Index (ASI) Alcohol Composite Total Score must fall between 0 and 1, and scores closer to 1 suggest continued problem drinking. | 12 weeks of treatment, with a follow-up one month after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol, treatment, nicotinic acetylcholine receptors, pharmacotherapy, outpatient