Varenicline for Smoking Reduction in Veterans Not Ready To Quit

August 26, 2026 updated by: VA Office of Research and Development

Varenicline for Smoking Reduction in Veterans Unwilling to Quit

In order to reduce the prevalence of cigarette smoking among Veterans, it is vital that healthcare providers offer effective tobacco treatment to all Veterans who smoke, including those not ready to make a quit attempt. Smoking treatments currently available to Veterans who are not ready to quit are only weakly effective. This project will generate new knowledge about the effectiveness of a promising varenicline-based intervention designed to increase quit attempts and long-term abstinence in Veterans who are initially not ready to quit. This project has great potential to engage Veterans not ready to quit smoking in treatment that increases quit attempts and quitting success, thereby reducing morbidity and mortality caused by smoking in Veterans.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Evidence-based smoking cessation treatments can double smoking abstinence rates, yet these treatments are underused by the millions of Veterans who smoke. One reason for this is that the great majority of people who smoke are not ready to make a quit attempt when cessation treatment is offered (70-90%). An important public health goal is to increase engagement of people not ready to quit smoking in highly effective treatment that prepares them to make quit attempts and ultimately achieve abstinence (i.e., Motivation-phase treatment; MPT). MPT typically combines smoking reduction counseling with nicotine replacement therapy (NRT). Although offering NRT Motivation-phase treatment (NRT MPT) in healthcare settings increases the reach of tobacco treatment, such interventions only weakly affect long-term abstinence. It is vital that the investigators develop more effective MPTs that increase quit attempts and quitting success in people not ready to quit. Varenicline, the most effective single agent smoking cessation pharmacotherapy, holds great promise as an intervention for people who are not ready to make a quit attempt. The investigators propose that MPT will be markedly more effective if it involves the use of varenicline (vs. NRT) because it will more effectively reduce smoking reward, affective withdrawal, and tonic craving. Initial evidence suggests that varenicline increases quitting motivation in those not ready to quit, but the extant studies have not 1) directly evaluated varenicline effectiveness in this population and 2) compared varenicline MPT with NRT MPT, the current standard treatment for those not ready to make a quit attempt. The goal of this study is to evaluate whether varenicline MPT is especially effective and cost-effective relative to NRT MPT, in Veterans who are willing to reduce but not quit smoking. This study will compare the use of varenicline MPT vs. NRT MPT on: biochemically verified point-prevalence abstinence at 1 year (primary outcome), quit attempts, and cessation treatment use.

This study is a 2-group randomized controlled trial that will enroll 400 adults from three geographically diverse VA hospitals who smoke 5 cigarettes/day and do not want to quit smoking in the next 30 days but are willing to cut down. Participants will be randomized to one of two 12-week MPT groups: (1) varenicline, or (2) NRT (2 milligrams (mg) mini-lozenges). All participants will receive 5 phone counseling sessions focused on smoking reduction during the 12-week MPT. Any participants who decide to try quitting will receive smoking cessation treatment involving continued use of their assigned study medication and cessation counseling.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92161-0002
        • Recruiting
        • VA San Diego Healthcare System, San Diego, CA
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417-2309
        • Recruiting
        • Minneapolis VA Health Care System, Minneapolis, MN
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27705-3875
        • Recruiting
        • Durham VA Medical Center, Durham, NC
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53705-2254
        • Active, not recruiting
        • William S. Middleton Memorial Veterans Hospital, Madison, WI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Report smoking an average of 5 or more cigarettes daily for the previous 6 months
  • Not ready to set a quit date in the next 30 days but willing to cut down on their smoking
  • Able to read, write, and speak English
  • Be medically eligible to use study medications (nicotine replacement therapy (NRT) or varenicline)
  • If female, use an approved method of birth control while using study medication
  • Be a Veteran

Exclusion Criteria:

  • Unable to give informed, voluntary consent to participate
  • Current use of any pharmacotherapy for smoking cessation
  • Use of non-cigarette tobacco products as primary form of tobacco use
  • Incarceration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Motivation-Phase Varenicline
Varenicline use during pre-quit phase of smoking treatment for participants who are interested in cutting down on their smoking.
Behavioral: Motivation-Phase Counseling
All participants receive motivation-phase counseling. Motivation-phase counseling involves 5, 10-15-minute counseling calls. The counselor will work with participants on smoking control skills selected by the participant, such as avoidance of smoking cues, reducing smoking heaviness/contexts, developing urge coping skills, or finding support from friends and family. Counseling will emphasize setting realistic and achievable smoking control goals. Counseling will also emphasize competence and self-efficacy, which will be linked to success in smoking control.
Behavioral: Cessation-Phase Counseling
All participants who enter cessation treatment will be offered 4, 10-15-minute counseling calls. The first counseling session involves pre-quit preparation, and can occur any time before the target quit day. The other 3 counseling calls will be scheduled for 1 day, 1 week, and 4 weeks after the target quit date. Cessation counseling will be based on treatment guidelines and will review instructions for when to start cessation medication, the timing of the quit day (relative to medication start), and medication adherence. Counseling will involve problem solving and skill development.
Drug: Motivation-Phase Varenicline
Varenicline reduction dosing will start when participants initiate Motivation-phase treatment: 0.5 milligrams (mg) once daily for 3 days, increasing to 0.5mg twice daily for days 4 to 7, and then to the maintenance dose of 1mg twice daily for the duration of the 12-week reduction regimen.
Other Names:
  • Chantix
Drug: Cessation-Phase Varenicline
Varenicline cessation dosing will start one week prior to their target quit date (TQD): 0.5 milligrams (mg) once daily for 3 days, increasing to 0.5mg twice daily for days 4 to 7, and then to the maintenance dose of 1mg twice daily for the remainder of the 12-week cessation regimen.
Other Names:
  • Chantix
Active Comparator: Motivation-Phase Nicotine Mini-Lozenge
NRT mini-lozenge use during pre-quit phase of smoking treatment for participants who are interested in cutting down on their smoking.
Behavioral: Motivation-Phase Counseling
All participants receive motivation-phase counseling. Motivation-phase counseling involves 5, 10-15-minute counseling calls. The counselor will work with participants on smoking control skills selected by the participant, such as avoidance of smoking cues, reducing smoking heaviness/contexts, developing urge coping skills, or finding support from friends and family. Counseling will emphasize setting realistic and achievable smoking control goals. Counseling will also emphasize competence and self-efficacy, which will be linked to success in smoking control.
Behavioral: Cessation-Phase Counseling
All participants who enter cessation treatment will be offered 4, 10-15-minute counseling calls. The first counseling session involves pre-quit preparation, and can occur any time before the target quit day. The other 3 counseling calls will be scheduled for 1 day, 1 week, and 4 weeks after the target quit date. Cessation counseling will be based on treatment guidelines and will review instructions for when to start cessation medication, the timing of the quit day (relative to medication start), and medication adherence. Counseling will involve problem solving and skill development.
Drug: Motivation-Phase Nicotine Mini-Lozenge
NRT mini-lozenge reduction dosing will start when participants initiate Motivation-phase treatment: 2-milligrams (mg) mini-lozenges in place of cigarettes (5-15/day).
Other Names:
  • Nicorette
Drug: Cessation-Phase Combination Nicotine Replacement Therapy (NRT)
Combination NRT (nicotine patch + nicotine mini-lozenge) cessation dosing will begin on the target quit day: if smoking >10 cigarettes/day = 8 weeks of 21-milligrams (mg), 2 weeks of 14-mg, and 2 weeks of 7-mg nicotine patches; if smoking 10 cigarettes/day = 10 weeks of 14-mg and 2 weeks of 7-mg nicotine patches. All participants will receive 2 or 4 mg mini-lozenge for the 12-week cessation period (9/day, 1 piece every 1-2/hours).
Other Names:
  • Nicorette, Nicoderm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
7-day point prevalence abstinence
Time Frame: 6 months post-study entry
Participants who report 7-day point-prevalence abstinence from cigarettes at the 6 month follow-up will mailed a saliva collection kit that will test cotinine and anabasine to validate self-reported abstinence from combusted tobacco.
6 months post-study entry

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemically confirmed 7-day point-prevalence abstinence
Time Frame: 12 months post-study entry
Participants who report 7-day point-prevalence abstinence from cigarettes at the 12 month follow-up will mailed a saliva collection kit that will test cotinine and anabasine to validate self-reported abstinence from combusted tobacco.
12 months post-study entry
Making a quit attempt lasting 24 hours
Time Frame: 6 and 12 months post-study entry
Making a quit attempt lasting at least 24 hours by 6 and 12 months; coded as binary (0 or 1).
6 and 12 months post-study entry
Cessation treatment entry
Time Frame: 6 months post-study entry
Entering cessation treatment; coded as binary (0 or 1)
6 months post-study entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Jessica Megan Cook, PhD, William S. Middleton Memorial Veterans Hospital, Madison, WI
  • Principal Investigator: Neal M Doran, PhD, VA San Diego Healthcare System, San Diego, CA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 17, 2026

Primary Completion (Estimated)

June 28, 2030

Study Completion (Estimated)

June 28, 2030

Study Registration Dates

First Submitted

May 2, 2025

First Submitted That Met QC Criteria

May 2, 2025

First Posted (Actual)

May 11, 2025

Study Record Updates

Last Update Posted (Actual)

August 31, 2026

Last Update Submitted That Met QC Criteria

August 26, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NURA-007-24F

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Deidentified dataset will be shared upon request.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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