Combining Varenicline and Naltrexone for Smoking Cessation

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.

Inclusion Criteria:

1. Be treatment-seeking for smoking cessation and have a desire to reduce or quit
drinking

2. Be between the ages of 21 and 65

3. Be able to provide informed consent

4. Smoke 5 or more cigarettes per day for the past year

5. 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

6. Pass the physical exam and associated laboratory tests, as determined by study
physician

Exclusion Criteria:

1. 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

2. Have lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, a psychotic
disorder, or any other psychiatric disorder as determined by the clinical interview

3. Have major depressive disorder within the past year requiring treatment as determined
by the clinical interview using DSM-V criteria

4. 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

5. Have a prior history of taking FDA approved medications (i.e. varenicline or
bupropion) for smoking cessation

6. Be currently using any forms of nicotine replacement therapy (past use is acceptable)

7. Be currently using tobacco products other than cigarettes (such as e-cigarettes,
cigars, or chewing tobacco)

8. Have a serious medical illness (significant cardiovascular disease; uncontrolled
hypertension; hepatic or renal disease) that would contraindicate participation, as
determined by the study physician

9. Be currently taking insulin or oral hypoglycemic medication

10. Be currently taking opioid pain medications or any form of opioid agonist maintenance
therapy (such as methadone or buprenorphine)

11. Be currently taking any other psychoactive medications; such as anti-depressants, mood
stabilizers, anti-seizure medications, sedatives-hypnotics, anxiolytics, stimulants or
antipsychotics

12. Have self-reported use of cocaine, methamphetamine, heroin or other illicit drugs in
the previous 60 days, verified by urine toxicology screen

13. 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