Naltrexone for At-Risk and Problem Drinking in Smoking Cessation Treatment

Study Overview
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Brief Summary
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To test whether naltrexone compared to placebo can reduce heavy drinking and improve smoking cessation outcomes in heavy drinkers seeking smoking cessation treatment.

Detailed Description
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A substantial portion of individuals seeking behavioral and pharmacological treatment for smoking cessation drink excessively with many reporting significant alcohol problems. Although these at-risk and problem drinkers are unlikely to choose abstinence from alcohol as a goal, many make substantial reductions in their drinking during and after their quit smoking attempt. Thus, the context of smoking cessation treatment offers a unique and valuable opportunity in which to apply brief interventions and pharmacotherapy to catalyze change in excessive drinking in a population with markedly elevated risk for negative health outcomes. In our recent randomized clinical trial, standard smoking cessation treatment that incorporated a brief alcohol intervention showed promise in reducing drinking as well as in improving smoking cessation outcomes among heavy drinkers. However, these effects were relatively modest, especially among the heaviest drinkers, indicating that further study is warranted of methods to address heavy drinking in smoking cessation including the use of relevant pharmacotherapy. Naltrexone, in particular, shows promise for this purpose. The overall aim of this project is to test the efficacy of naltrexone as a pharmacotherapy for excessive drinking when delivered to at-risk or problem drinkers who are seeking smoking cessation treatment. The proposed clinical trial uses a between-subjects design in which 300 at-risk or problem drinkers seeking treatment for smoking cessation will be randomly assigned to receive either daily 50 mg naltrexone or placebo. Medication will be initiated 2 weeks prior to participants' smoking quit date and continue for 10 weeks. All participants also will receive transdermal nicotine patch and a counseling and medication management intervention that provides advice for smoking cessation, advice regarding the effects of heavy drinking on both smoking cessation and health, and monitoring and encouragement of compliance with medications. Drinking and smoking outcomes will be assessed at 2, 8, 16, and 26 weeks after participants' smoking quit date. The primary aim of the study is to test the hypothesis that naltrexone will result in greater reductions in heavy drinking relative to placebo. The secondary aim will test whether naltrexone results in superior smoking outcomes relative to placebo, and tertiary aims will examine interrelationships among motivation for changing drinking, compliance with naltrexone, and drinking and smoking outcomes. This study represents the first of its kind to provide naltrexone in conjunction with an opportunistic brief alcohol intervention for at-risk and problem drinkers not seeking alcohol treatment. Testing the potential benefits of naltrexone among at-risk and problem drinkers who smoke is of very high significance for public health efforts to reduce the markedly elevated rates of morbidity and mortality observed in this large, yet relatively understudied group.

Official Title
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Naltrexone for At-Risk and Problem Drinking in Smoking Cessation Treatment

Conditions
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Hazardous Drinking, Cigarette Smoking

Intervention / Treatment
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* Drug: Naltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.) be at least 18 years of age, 2.) drink heavily at least once per month on average (≥4 drinks per occasion for women; ≥5 drinks for men), 3.) have smoked cigarettes regularly for at least one year, 4.) currently smoke at least 5 cigarettes a day, 5.) currently be using no other tobacco products or nicotine replacement therapy Exclusion Criteria: 1.) meet criteria for current substance dependence (excluding nicotine and alcohol); 2.) report opiate use in the past month, have a drug screen positive for opiates, or require opiate containing medications for pain management; 3.) meet criteria for a current major depressive or manic episode; 4.) are currently psychotic or suicidal; 5.) have an unstable or serious medical condition that would preclude use of the nicotine patch or naltrexone (e.g., unstable angina pectoris, severe arrhythmia, recent congestive heart failure); 6.) have aspartate aminotransferase or alanine aminotransferase levels of more than 3 times the reference range or elevated bilirubin levels; or 7.) are currently pregnant or lactating, intend to become pregnant, or are not using a reliable means of birth control.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Naltrexone<br>50 mg daily naltrexone for 10 weeks | Drug: Naltrexone<br>* Daily 50 mg naltrexone<br>|
| Placebo Comparator: Placebo<br>Daily matched placebo pill | Drug: Placebo<br>* Matched naltrexone placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Heavy Drinking Days | Defined for women as percent of days drinking 4 or more drinks in a day. For men, percent of days drinking 5 or more drinks in a day | Across the 6 months following smoking quit date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point Prevalence Smoking Abstinence | Self-report abstinence from smoking over the past 7 days biochemically confirmed with carbon monoxide and saliva cotinine. | 26 weeks after target quit smoking date |