Varenicline for Smoking Reduction in Veterans Not Ready To Quit

NCT ID: NCT06966362

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-01
• Study Completion Date: 2031-03-31

Brief Summary

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.

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 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.

Conditions

Veterans; Tobacco Use Disorder; Cigarette Smoking; Tobacco Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Motivation-Phase Varenicline

Varenicline use during pre-quit phase of smoking treatment for participants who are interested in cutting down on their smoking.

Group Type: EXPERIMENTAL

Motivation-Phase Varenicline

Intervention Type: DRUG

Varenicline reduction dosing will start when participants initiate Motivation-phase treatment: 0.5mg 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.

Cessation-Phase Varenicline

Intervention Type: DRUG

Varenicline cessation dosing will start one week prior to their TQD: 0.5mg 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.

Motivation-Phase Counseling

Intervention Type: BEHAVIORAL

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.

Cessation-Phase Counseling

Intervention Type: BEHAVIORAL

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.

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.

Group Type: ACTIVE_COMPARATOR

Motivation-Phase Nicotine Mini-Lozenge

Intervention Type: DRUG

NRT mini-lozenge reduction dosing will start when participants initiate Motivation-phase treatment: 2-mg mini-lozenges in place of cigarettes (5-15/day).

Cessation-Phase Combination Nicotine Replacement Therapy (NRT)

Intervention Type: DRUG

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-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).

Motivation-Phase Counseling

Intervention Type: BEHAVIORAL

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.

Cessation-Phase Counseling

Intervention Type: BEHAVIORAL

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.

Interventions

Motivation-Phase Varenicline

Varenicline reduction dosing will start when participants initiate Motivation-phase treatment: 0.5mg 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.

Intervention Type: DRUG

Motivation-Phase Nicotine Mini-Lozenge

NRT mini-lozenge reduction dosing will start when participants initiate Motivation-phase treatment: 2-mg mini-lozenges in place of cigarettes (5-15/day).

Intervention Type: 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-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).

Intervention Type: DRUG

Cessation-Phase Varenicline

Varenicline cessation dosing will start one week prior to their TQD: 0.5mg 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.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Chantix; Nicorette; Nicorette, Nicoderm; Chantix

Eligibility Criteria

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 (NRT or varenicline)
• If female, use an approved method of birth control while using study medication
• Be at least 21 years old
• 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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jessica Megan Cook, PhD

Role: PRINCIPAL_INVESTIGATOR

William S. Middleton Memorial Veterans Hospital, Madison, WI

Neal M Doran, PhD

Role: PRINCIPAL_INVESTIGATOR

VA San Diego Healthcare System, San Diego, CA

Locations

VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, United States

Countries

United States

Central Contacts

Jessica M Cook, PhD

Role: CONTACT

Jessica.Cook2@va.gov

(608) 256-1901

Elana G Brubaker, MSW BS

Role: CONTACT

elana.brubaker@va.gov

(608) 256-1901 ext. 17854

Facility Contacts

Neal Doran, PhD

Role: primary

neal.doran@va.gov

Patrick Hammett, PhD

Role: primary

patrick.hammett@va.gov

Jean Beckham, PhD

Role: primary

jean.beckham@va.gov

Jessica M Cook, PhD

Role: primary

Jessica.Cook2@va.gov

(608) 256-1901

Aaron F Heneghan, PhD

Role: backup

Aaron.Heneghan@va.gov

(608) 256-1901 ext. 17801

Other Identifiers

NURA-007-24F

Identifier Type: -

Identifier Source: org_study_id