The Avenues Study: Dual Use Cessation

Dual Use Cessation: A MOST Screening Trial to Identify Effective Interventions to Help People Who Smoke and Vape

The overarching goal of this research is to determine the most effective approach for helping dual users of cigarettes and electronic nicotine delivery systems (ENDS) quit smoking. 500 participants will be enrolled and can expect to be on study for 12 months.

Study Overview

• Status: Recruiting
• Conditions: Smoking Cessation; Electronic Cigarette Use
• Intervention / Treatment: Drug: Varenicline; Behavioral: Dual Focused Cessation Counseling; Behavioral: Smoking Focused Cessation Counseling; Drug: Nicotine patch; Other: Counseling Intensity: 1 Session; Other: Counseling Intensity: 4 Sessions

Detailed Description

To be efficient and maximize translation potential, the investigators will use the efficient Multiphase Optimization Strategy (MOST) to identify an optimal intervention to help people who use both cigarettes and ENDS quit smoking cigarettes. As such, in this randomized 2x2x2 factorial screening trial, the investigators will examine three intervention components:

1. Pharmacotherapy (varenicline vs. nicotine patch)
2. Counseling Intensity (4 vs. 1 session)
3. Counseling Approach (Dual Focused vs. Smoking Focused).

The Dual Focused counseling approach will encourage participants to quit their ENDS use as part of their smoking cessation attempt. The Smoking Focused counseling approach will encourage participants to quit smoking but not vaping and to use their ENDS strategically to deal with urges in service of harm reduction. There is theoretical and empirical support for these pharmacologic and counseling approaches and intensities.

Participants (N=500) will be dual users of cigarettes (>4 cigs/day for the last 6 months) and ENDS (vape weekly for at least 6 months) who are motivated to quit smoking and willing try to quit vaping, if asked to do so. Participants will be recruited, assessed, and treated remotely. They will be randomized to receive either varenicline or nicotine patches for 12 weeks, to receive either one or four 15-20-minute counseling sessions, and to receive counseling that is either dual focused or smoking focused. Dual Focused Cessation will focus on quitting both smoking and vaping on the target quit date (TQD). Pre-TQD, participants will be instructed to change smoking and vaping patterns (e.g., not smoking or vaping in specific places or at specific times of day). Post-TQD, participants will focus on building smoking and vaping cessation skills (e.g., coping with cravings to smoke or vape, avoiding smoking and vaping cues). Smoking Focused Cessation will focus on quitting smoking on the TQD and using ENDS as a behavioral substitute (i.e., using ENDS as a cigarette substitute). Pre-TQD, participants will be instructed to change smoking patterns (e.g., vaping rather than smoking in specific places or at specific times of day, vaping first in the morning rather than smoking) and practice smoking cessation coping strategies (e.g., substituting ENDS for cigarettes, avoiding smoking cues). Participants will be advised to quit smoking on the TQD and not worry about quitting vaping at this point. Participants will complete daily measures of smoking, vaping, and potential change mechanisms (e.g., craving, smoking reward, self-efficacy) via ecological momentary assessment (EMA) for 2 weeks pre-TQD and 2 weeks post-TQD. Follow-up will occur for 12 months post-TQD.

Primary Objective: Determine which pharmacologic and counseling approaches are especially effective, alone or in combination, in helping dual users quit smoking.

Secondary Objectives:

• Examine the effects of the treatments on variables that may mediate treatment effects on smoking cessation.

• Examine

  1. changes in vaping intensity and vaping cessation
  2. moderators of treatment effects (e.g., cigarette dependence, race, menthol use, ENDS characteristics), and
  3. whether continued vaping is related to cigarette lapse and relapse amongst those who have quit smoking.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mark Zehner; Phone Number: 608-262-7568; Email: mark.zehner@wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin-Madison School of Medicine and Public Health
      • Principal Investigator: Megan Piper, PhD
      • Contact: Mark Zehner; Phone Number: 608-262-7568; Email: mark.zehner@wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to read and communicate in English
• Willing to set a quit date to quit smoking cigarettes in the next 30 days
• Willing and medically able to use varenicline and nicotine patches
• Smoking ≥ 5 cigarettes per day for the past 6 months
• Vaping weekly for at least 6 months
• Willing to stop using nicotine replacement or varenicline
• Willing to stop using bupropion (i.e., Wellbutrin, Zyban) if they are currently using it only for smoking cessation
• Saliva cotinine >20 ng/ml
• US resident
• Own a Smartphone to use and download an app to record data
• have a working email so that they can receive links for video visits

Exclusion Criteria:

• Currently in treatment for psychosis or bipolar disorder
• If they are currently taking bupropion for non-smoking cessation reasons (e.g., Wellbutrin for depression)
• Currently pregnant or breastfeeding. If a participant becomes pregnant while in the study, they will be allowed to continue in the study but will no longer receive study medications. They will also be asked to return any unused study medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Varenicline, Dual Focused, 1 session	Drug: Varenicline; 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (at least 8 hours apart) for 4 days prior to the TQD. On the 8th day (the TQD), participants will increase to their target maintenance dose of a 1 mg pill twice daily; Behavioral: Dual Focused Cessation Counseling; Dual Focused Cessation Counseling will focus on quitting both smoking and vaping. Specifically, participants will be instructed to change smoking and vaping patterns (e.g., not smoking or vaping in specific places such as the car or at specific times of day) prior to quitting and to practice cessation coping strategies (e.g., distraction techniques, getting social support).; Other: Counseling Intensity: 1 Session; Participants assigned to one session will complete a single, 15-20 minute, session at Visit 2 (1 week pre-TQD).
Active Comparator: Varenicline, Dual Focused, 4 sessions	Drug: Varenicline; 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (at least 8 hours apart) for 4 days prior to the TQD. On the 8th day (the TQD), participants will increase to their target maintenance dose of a 1 mg pill twice daily; Behavioral: Dual Focused Cessation Counseling; Dual Focused Cessation Counseling will focus on quitting both smoking and vaping. Specifically, participants will be instructed to change smoking and vaping patterns (e.g., not smoking or vaping in specific places such as the car or at specific times of day) prior to quitting and to practice cessation coping strategies (e.g., distraction techniques, getting social support).; Other: Counseling Intensity: 4 Sessions; Participants assigned to intensive counseling will have four, 15-20-minute sessions.
Active Comparator: Varenicline, Smoking Focused, 1 session	Drug: Varenicline; 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (at least 8 hours apart) for 4 days prior to the TQD. On the 8th day (the TQD), participants will increase to their target maintenance dose of a 1 mg pill twice daily; Behavioral: Smoking Focused Cessation Counseling; Smoking Focused Cessation Counseling will focus on quitting smoking and using ENDS as a harm reduction strategy (i.e., using ENDS as a substitute for cigarettes).; Other: Counseling Intensity: 1 Session; Participants assigned to one session will complete a single, 15-20 minute, session at Visit 2 (1 week pre-TQD).
Active Comparator: Varenicline, Smoking Focused, 4 sessions	Drug: Varenicline; 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (at least 8 hours apart) for 4 days prior to the TQD. On the 8th day (the TQD), participants will increase to their target maintenance dose of a 1 mg pill twice daily; Behavioral: Smoking Focused Cessation Counseling; Smoking Focused Cessation Counseling will focus on quitting smoking and using ENDS as a harm reduction strategy (i.e., using ENDS as a substitute for cigarettes).; Other: Counseling Intensity: 4 Sessions; Participants assigned to intensive counseling will have four, 15-20-minute sessions.
Active Comparator: Nicotine Patches, Dual Focused, 1 session	Behavioral: Dual Focused Cessation Counseling; Dual Focused Cessation Counseling will focus on quitting both smoking and vaping. Specifically, participants will be instructed to change smoking and vaping patterns (e.g., not smoking or vaping in specific places such as the car or at specific times of day) prior to quitting and to practice cessation coping strategies (e.g., distraction techniques, getting social support).; Drug: Nicotine patch; Following package inserts starting on the TQD, participants who smoke >10 cigarettes per day at baseline will be given 8 weeks of 21 mg nicotine patches, followed by 2 weeks of 14 mg patches, and 2 weeks of 7 mg patches. Participants who smoke ≤10 cigarettes per day at baseline will be given 10 weeks of 14 mg nicotine patches followed by 2 weeks of 7 mg patches.; Other: Counseling Intensity: 1 Session; Participants assigned to one session will complete a single, 15-20 minute, session at Visit 2 (1 week pre-TQD).
Active Comparator: Nicotine Patches, Dual Focused, 4 sessions	Behavioral: Dual Focused Cessation Counseling; Dual Focused Cessation Counseling will focus on quitting both smoking and vaping. Specifically, participants will be instructed to change smoking and vaping patterns (e.g., not smoking or vaping in specific places such as the car or at specific times of day) prior to quitting and to practice cessation coping strategies (e.g., distraction techniques, getting social support).; Drug: Nicotine patch; Following package inserts starting on the TQD, participants who smoke >10 cigarettes per day at baseline will be given 8 weeks of 21 mg nicotine patches, followed by 2 weeks of 14 mg patches, and 2 weeks of 7 mg patches. Participants who smoke ≤10 cigarettes per day at baseline will be given 10 weeks of 14 mg nicotine patches followed by 2 weeks of 7 mg patches.; Other: Counseling Intensity: 4 Sessions; Participants assigned to intensive counseling will have four, 15-20-minute sessions.
Active Comparator: Nicotine Patches, Smoking Focused, 1 session	Behavioral: Smoking Focused Cessation Counseling; Smoking Focused Cessation Counseling will focus on quitting smoking and using ENDS as a harm reduction strategy (i.e., using ENDS as a substitute for cigarettes).; Drug: Nicotine patch; Following package inserts starting on the TQD, participants who smoke >10 cigarettes per day at baseline will be given 8 weeks of 21 mg nicotine patches, followed by 2 weeks of 14 mg patches, and 2 weeks of 7 mg patches. Participants who smoke ≤10 cigarettes per day at baseline will be given 10 weeks of 14 mg nicotine patches followed by 2 weeks of 7 mg patches.; Other: Counseling Intensity: 1 Session; Participants assigned to one session will complete a single, 15-20 minute, session at Visit 2 (1 week pre-TQD).
Active Comparator: Nicotine Patches, Smoking Focused, 4 sessions	Behavioral: Smoking Focused Cessation Counseling; Smoking Focused Cessation Counseling will focus on quitting smoking and using ENDS as a harm reduction strategy (i.e., using ENDS as a substitute for cigarettes).; Drug: Nicotine patch; Following package inserts starting on the TQD, participants who smoke >10 cigarettes per day at baseline will be given 8 weeks of 21 mg nicotine patches, followed by 2 weeks of 14 mg patches, and 2 weeks of 7 mg patches. Participants who smoke ≤10 cigarettes per day at baseline will be given 10 weeks of 14 mg nicotine patches followed by 2 weeks of 7 mg patches.; Other: Counseling Intensity: 4 Sessions; Participants assigned to intensive counseling will have four, 15-20-minute sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
52-week biochemically confirmed 7-day point-prevalence abstinence from cigarettes	52-week biochemically confirmed (anabasine<2 ng/ml) 7-day point-prevalence abstinence from cigarettes	up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day point-prevalence abstinence from smoking and vaping at Weeks 26 and 52 post-TQD	Biochemically confirmed with saliva cotinine <30 ng/mL	up to 52 weeks
26-week biochemically confirmed 7-day point-prevalence abstinence from cigarettes	26-week biochemically confirmed (anabasine<2 ng/ml) 7-day point-prevalence abstinence from cigarettes	up to 26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving Initial Smoking Abstinence	Measured by self-reported 24-hours of cigarette abstinence within the first 2 weeks of the target quit day	up to 2 weeks
7-day point-prevalence abstinence from smoking and vaping at Week 12	Biochemically confirmed with saliva cotinine <30 ng/mL	up to 12 Weeks (end of treatment)
Number of Participants Achieving Initial Abstinence from Smoking and Vaping	Measured by self-reported 24-hours of cigarette and ENDS abstinence within the first 2 weeks of the target quit day	up to 2 weeks
Number of days until first cigarette following initial cessation	Latency to lapse (number of days until first cigarette following initial cessation) computed over the full 52 weeks post-TQD	up to 52 weeks post-TQD
Number of days until 7 consecutive days of smoking following initial cessation	Latency to relapse (number of days until 7 consecutive days of smoking following initial cessation) computed over the full 52 weeks post-TQD.	up to 52 weeks post-TQD
12-week biochemically confirmed 7-day point-prevalence abstinence from cigarettes	12-week biochemically confirmed (anabasine<2 ng/ml) 7-day point-prevalence abstinence from cigarettes	up to 12 Weeks (end of treatment)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Megan E Piper, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cessation; ENDS
• Additional Relevant MeSH Terms: Behavior; Smoking; Health Behavior; Vaping; Smoking Cessation; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Benzazepines; Quinoxalines; Varenicline; Tobacco Use Cessation Devices
• Other Study ID Numbers: 2024-0019; A534253 (Other Identifier: UW- Madison); SMPH/MEDICINE/GEN INT MD (Other Identifier: UW Madison); R01CA290895 (U.S. NIH Grant/Contract); Protocol Version 12/12/2025 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No