Varenicline Treatment of Alcohol Dependence in Smokers

• ClinicalTrials.gov Identifier: NCT01553136
• Recruitment Status: Completed
• First Posted: March 13, 2012
• Results First Posted: February 12, 2018
• Last Update Posted: March 6, 2020
• Sponsor: Yale University
• Collaborators: Columbia University; National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alcoholism; Alcohol Abuse; Smoking; Alcohol Drinking	Drug: Varenicline	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 1/2-Multi-site Study: Varenicline Treatment of Alcohol Dependent Smokers
• Study Start Date: September 2012
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: May 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Sugar pill	Drug: Varenicline; 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; Other Name: Chantix
Active Comparator: Varenicline	Drug: Varenicline; 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; Other Name: Chantix

Outcome Measures

Primary Outcome Measures :

1. Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment [ Time Frame: weeks 9-12 ]
   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.
2. Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment [ Time Frame: weeks 13-16 ]
   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.
3. Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment [ Time Frame: 8 weeks ]
   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).

Secondary Outcome Measures :

1. Smoking Abstinence [ Time Frame: Weeks 13-16 ]
   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.
2. Drinking Related Consequences [ Time Frame: End of treatment (Week 17) ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

United States, Connecticut

Connecticut Mental Health Center - Substance Abuse Treatment Unit

New Haven, Connecticut, United States, 06511

United States, New York

Parallax Center

New York, New York, United States, 10016

Sponsors and Collaborators

Yale University

Columbia University

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Stephanie O'Malley, PhD; Yale University
• Principal Investigator: Allen Zweben, PhD; Columbia University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bold KW, Zweben A, Fucito LM, Piepmeier ME, Muvvala S, Wu R, Gueorguieva R, O'Malley SS. Longitudinal Findings from a Randomized Clinical Trial of Varenicline for Alcohol Use Disorder with Comorbid Cigarette Smoking. Alcohol Clin Exp Res. 2019 May;43(5):937-944. doi: 10.1111/acer.13994. Epub 2019 Mar 21.

O'Malley SS, Zweben A, Fucito LM, Wu R, Piepmeier ME, Ockert DM, Bold KW, Petrakis I, Muvvala S, Jatlow P, Gueorguieva R. Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):129-138. doi: 10.1001/jamapsychiatry.2017.3544.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01553136
• Other Study ID Numbers: 1106008598; 1R01AA020388-01A1 ( U.S. NIH Grant/Contract )
• First Posted: March 13, 2012
• Results First Posted: February 12, 2018
• Last Update Posted: March 6, 2020
• Last Verified: October 2018

Keywords provided by Yale University:

alcohol-related disorders; Cholinergic Drugs; varenicline; Chantix

Additional relevant MeSH terms:

Alcoholism; Alcohol Drinking; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs