Combining Varenicline and Naltrexone for Smoking Cessation

Combining Varenicline and Naltrexone for Smoking Cessation and Drinking Reduction

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder; Nicotine Dependence
• Intervention / Treatment: Drug: Varenicline plus Naltrexone; Drug: Varenicline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Addictions Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Varenicline plus Naltrexone; VAR (1 mg twice daily) + NTX (50 mg once daily)	Drug: Varenicline plus Naltrexone; Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily; Other Names: Revia; Chantix
Placebo Comparator: Varenicline; VAR (1 mg twice daily)	Drug: Varenicline; Varenicline 1 mg twice daily; Other Names: Chantix

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute on Drug Abuse (NIDA)

Publications and helpful links

General Publications

• Green R, Montoya AK, Ray LA. The relationship between drinking and smoking in a clinical trial for smoking cessation and drinking reduction. Exp Clin Psychopharmacol. 2022 Dec;30(6):873-883. doi: 10.1037/pha0000536. Epub 2021 Dec 30.
• Ray LA, Green R, Enders C, Leventhal AM, Grodin EN, Li G, Lim A, Hartwell E, Venegas A, Meredith L, Nieto SJ, Shoptaw S, Ho D, Miotto K. Efficacy of Combining Varenicline and Naltrexone for Smoking Cessation and Drinking Reduction: A Randomized Clinical Trial. Am J Psychiatry. 2021 Sep 1;178(9):818-828. doi: 10.1176/appi.ajp.2020.20070993. Epub 2021 Jun 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: February 19, 2016
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimate): March 3, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Sensory System Agents; Narcotic Antagonists; Nicotinic Agonists; Cholinergic Agonists; Alcohol Deterrents; Naltrexone; Varenicline
• Other Study ID Numbers: VAR-NTX; R01DA041226 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No