Combining Varenicline and Naltrexone for Smoking Cessation

Study Overview
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Brief Summary
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This study is a double-blind, randomized clinical trial using a two group medication design consisting of the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) and VAR (1 mg twice daily) + PLA (matched to NTX), for smoking cessation in a sample of heavy drinking daily smokers who want to quit smoking and reduce drinking.

Detailed Description
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This study is a double-blind, randomized clinical trial using a two group medication design consisting of the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) and VAR (1 mg twice daily) + PLA (matched to NTX), for smoking cessation in a sample of heavy drinking daily smokers who want to quit smoking and reduce drinking. All participants will be daily smokers (≥ 5 cig/day) who are also heavy drinkers according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines: for men, > 14 drinks per week or ≥ 5 drinks per occasion at least once per month over the past 12 months; for women, > 7 drinks per week or ≥ 4 drinks per occasion at least once per month over the past 12 months. A total of 274 participants will be randomized, 137 to each medication group.

Official Title
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Combining Varenicline and Naltrexone for Smoking Cessation and Drinking Reduction

Conditions
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Nicotine Dependence, Alcohol Use Disorder

Intervention / Treatment
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* Drug: Varenicline
* Drug: Varenicline plus Naltrexone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be treatment-seeking for smoking cessation and have a desire to reduce or quit drinking Be between the ages of 21 and 65 Be able to provide informed consent Smoke 5 or more cigarettes per day for the past year Currently drink heavily according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines: for men, > 14 drinks per week or ≥ 5 drinks per occasion at least once per month over the past 12 months; for women, > 7 drinks per week or ≥ 4 drinks per occasion at least once per month over the past 12 months Pass the physical exam and associated laboratory tests, as determined by study physician Exclusion Criteria: Have clinically significant alcohol withdrawal, indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) and assessed at the in-person screening visits Have lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, a psychotic disorder, or any other psychiatric disorder as determined by the clinical interview Have major depressive disorder within the past year requiring treatment as determined by the clinical interview using DSM-V criteria Have a current or lifetime DSM-V diagnosis of a substance use disorder, other than for alcohol or nicotine, as determined by the clinical interview Have a prior history of taking FDA approved medications (i.e. varenicline or bupropion) for smoking cessation Be currently using any forms of nicotine replacement therapy (past use is acceptable) Be currently using tobacco products other than cigarettes (such as e-cigarettes, cigars, or chewing tobacco) Have a serious medical illness (significant cardiovascular disease; uncontrolled hypertension; hepatic or renal disease) that would contraindicate participation, as determined by the study physician Be currently taking insulin or oral hypoglycemic medication Be currently taking opioid pain medications or any form of opioid agonist maintenance therapy (such as methadone or buprenorphine) Be currently taking any other psychoactive medications; such as anti-depressants, mood stabilizers, anti-seizure medications, sedatives-hypnotics, anxiolytics, stimulants or antipsychotics Have self-reported use of cocaine, methamphetamine, heroin or other illicit drugs in the previous 60 days, verified by urine toxicology screen For women, must not be pregnant (as indicated by self-report or a positive pregnancy test at any study visit), nursing, or planning to become pregnant while taking part in the study, and must agree to a reliable method of birth control

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: Varenicline plus Naltrexone<br>VAR (1 mg twice daily) + NTX (50 mg once daily) | Drug: Varenicline plus Naltrexone<br>* Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily<br>* Other names: Revia;|
| Placebo Comparator: Varenicline<br>VAR (1 mg twice daily) | Drug: Varenicline<br>* Varenicline 1 mg twice daily<br>* Other names: Chantix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Expired Carbon Monoxide Level <=5ppm | Outcome for smoking cessation aim was Expired Carbon Monoxide level, which was used to determine whether a participant successfully abstained from cigarettes. 7 day point prevalence of nicotine abstinence was bioverified by Expired Carbon Monoxide reading of <= 5ppm at the 26-week follow-up visit. | 26 weeks post-quit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drinks Per Drinking Day | Outcome for drinking reduction aim - Number of Drinks per Drinking Day | 26 weeks post-quit |