Varenicline Treatment of Alcohol Dependence in Smokers

Study Overview
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Brief Summary
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The purpose of this study is to determine whether varenicline is effective in the treatment of alcohol dependence in smokers.

Detailed Description
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Building upon knowledge about the role of nicotinic acetylcholine receptors in alcohol drinking and smoking, varenicline, a smoking cessation treatment that targets these receptors, will be tested as a potential treatment for alcohol dependent smokers seeking alcohol treatment.

Official Title
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1/2-Multi-site Study: Varenicline Treatment of Alcohol Dependent Smokers

Conditions
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Alcoholism, Alcohol Abuse, Smoking, Alcohol Drinking

Intervention / Treatment
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* Drug: Varenicline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: are 18 - 70 years of age and seeking treatment of alcohol drinking; meet DSM-IV TR Criteria for Alcohol Dependence report smoking 100 cigarettes or more in their lifetime and currently smoke at least twice weekly on average in the past 90 days and have a urinary cotinine level of > 30ng/mL by semi-quantitative urinalysis or equivalent plasma cotinine level (> 6 ng/mL); report heavy drinking on at least 2 days on average per week (i.e., ≥ 4 drinks on an occasion for women and ≥ 5 drinks for men) for the past 90 days and no more than 7 consecutive days of abstinence at intake. Exclusion Criteria: exhibit current, clinically significant physical disease or abnormality based on medical history, physical examination, or routine laboratory evaluation including: any unexplained elevations in liver enzymes (i.e., transaminases, bilirubin) clinically significant, unstable cardiovascular disease/uncontrolled hypertension hepatic or renal impairment severe obstructive pulmonary disease diabetes mellitus requiring insulin or certain oral medications (i.e., sulfonylureas) and an A1C hemoglobin test score of > 7 for participants not prescribed these medications baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg have a history of cancer (except treated basal cell or squamous cell carcinoma of the skin) have a history of serious hypersensitivity reactions or skin reactions to varenicline; exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe major depression, panic disorder, borderline personality disorder, organic mood or mental disorders by history or psychological examination report current suicidal ideation (past 6 months) or lifetime hx of suicidal behavior assessed with the Columbia Suicide Severity Rating Scale 60; or risk for aggression using a cut-off of 15 or more on the Overt Aggression Scale - Modified Aggression Scale or 6 or more on the OAS-M Irritability Subscale 61. have used any psychotropic drug in the past month, except individuals who are on a stable dose of a Selective Serotonin Reuptake Inhibitor for at least two months or who report occasional use of prescription sleep aids that they are willing to discontinue; have a current DSM-IV diagnosis of drug dependence other than nicotine or alcohol are at risk for an alcohol withdrawal syndrome as evidenced by: a history of seizures, delirium, or hallucinations during alcohol withdrawal a Clinical Institute Withdrawal Assessment scale 62 score of > 8, report drinking to avoid withdrawal symptoms have required medical treatment of alcohol withdrawal within the past 6 months have used another investigational drug within 30 days or have used medications to treat alcohol (e.g., naltrexone, topiramate, acamprosate, disulfiram) or nicotine use (e.g., clonidine, varenicline, bupropion, nicotine replacement) in the past 3 months or intend to use these medications;prior use of nicotine replacement in situations where smoking is not permitted (e.g., planes) without the intention to quit smoking is not exclusionary; intend to donate blood or blood products during the treatment phase of the study have a Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) less than 15 or greater than 39.99 or weight less than 45 kg; are a female of childbearing potential who is pregnant, nursing, or not practicing effective contraception (oral, injectable, or implantable contraceptives, intrauterine device, or barrier method with spermicide).

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar pill<br> | Drug: Varenicline<br>* 0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then two 0.5 mg tablets (1 mg) twice per day<br>* Other names: Chantix;|
| Active Comparator: Varenicline<br> | Drug: Varenicline<br>* 0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then two 0.5 mg tablets (1 mg) twice per day<br>* Other names: Chantix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol. | weeks 9-12 | 
| Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol. | weeks 13-16 | 
| Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | The percentage of days of heavy drinking will be examined over the final 8 weeks of the study. A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol. Presented here is the average of the 8 weeks (reported as week 17 originally). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Abstinence | Smoking abstinence is defined by self-reported abstinence from smoking for the last four weeks of treatment (weeks 13-16) and a urine cotinine level less than 15ng/mL measured at week 17. | Weeks 13-16 | 
| Drinking Related Consequences | A self-report measure of negative consequences from drinking will be administered and the total score are analyzed. The ImBIBe, a measure of alcohol consequences based on the Drinker Inventory of Consequences (DRINC) was used. The DRINC total score has a range from 0-45, 45 being the highest score (or greatest number of negative consequences). | End of treatment (Week 17) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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varenicline, alcohol-related disorders, Cholinergic Drugs, Chantix