Trial of Varenicline With Nicotine Lozenges and a Smartphone Medication Adherence Intervention for Smoking Cessation

NCT07099638 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB 17722R01CA298165
• Study Type: interventional
• Target: 496
• Locations: 1 country
• Sites: 1

Brief Summary

Although the prevalence of smoking has declined among U.S. adults, smoking remains the leading preventable cause of cancer incidence and mortality. Quitting smoking increases life expectancy, and quitting at an earlier age is associated with more years of life gained. Effective pharmacotherapies to aid cessation are available, and the combination of behavioral support with pharmacotherapy optimizes cessation outcomes. Varenicline is an effective, first-line smoking cessation treatment, and recent research has investigated combination pharmacotherapy to improve the modest quit rates observed with monotherapy. The findings of two meta-analyses have indicated that varenicline combined with the nicotine patch was more effective than varenicline alone for smoking cessation However, no published studies to date have evaluated the combined impact of varenicline and oral nicotine replacement therapy (NRT) on smoking cessation in a randomized trial. Oral NRT, such as nicotine lozenges, can provide acute relief from cravings/withdrawal, and offers individuals the flexibility to deliver nicotine quickly, in contrast with the continuous, passive, and slow-acting delivery of the nicotine patch. Nevertheless, in clinical trials of other combination pharmacotherapies, participants' adherence to of oral NRT has been suboptimal, making it difficult to determine whether there is an added benefit. Given the near-ubiquity of smartphone ownership (85% of U.S. adults), it is plausible that smartphone-based medication adherence interventions could have a positive influence on pharmacotherapy adherence and smoking cessation. This investigative team has demonstrated the feasibility and potential efficacy of using combination varenicline plus oral NRT treatment to promote smoking cessation in a pilot factorial randomized trial. Likewise, pilot findings showed that medication adherence and smoking cessation rates were higher among those who received smartphone-based medication reminders than those who did not. The proposed study will enroll 496 adults who smoke cigarettes daily. The study will employ a 2x2 factorial design in which participants will be randomized to one of four combinations of two treatment factors: 1) pharmacological treatment (varenicline + nicotine lozenges vs. varenicline alone) and 2) smartphone medication adherence intervention (smartphone-based smoking cessation app with vs. without adherence components). The primary study outcomes will be biochemically-confirmed 7-day point prevalence abstinence at 26 weeks after a scheduled quit date, and medication adherence over the 13-week treatment period. Smartphone-based daily diaries will be employed to assess daily smoking and medication adherence. Notably, the proposed study will employ entirely remote assessment and treatment delivery strategies. Exploratory analyses will evaluate the potential interaction between medication type and the smartphone adherence intervention, and compare the influences of pharmacological treatment type and the medication adherence intervention on weekly physical symptoms (e.g., withdrawal, medication side effects). The overarching goal of the proposed research is to improve smoking cessation treatment and decrease cancer risk.

Conditions

Smoking Cessation

Keywords

Smoking Cessation; Varenicline; Nicotine Lozenges; Medication Adherence; Smartphone Intervention

Outcome Measures

Primary Outcomes (1)

• Smoking Abstinence (26 weeks post-quit)

  Self-reported smoking abstinence over the past 7 days with breath CO≤6 ppm

  26 weeks after the scheduled quit day

Secondary Outcomes (3)

• Medication Adherence (weekly)

  Weekly starting on the quit day (for varenicline) or 1-week post-quit (for lozenges) through 12 weeks post-quit.

• Medication Adherence (daily)

  Assessments begin 1 week before the quit day (varenicline) or on the quit day (lozenges) through 12 weeks post-quit.

• Smoking Abstinence (12 weeks post-quit)

  12 weeks after the scheduled quit day

Study Arms (4)

Varenicline + Smartphone Intervention with adherence components (VAR + ADHERE)

EXPERIMENTAL

Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.

Drug: Varenicline (VAR); Behavioral: Smartphone intervention with adherence components (ADHERE); Behavioral: Telephone Counseling

Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + ADHERE)

EXPERIMENTAL

Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.

Drug: Varenicline (VAR); Drug: Nicotine lozenge (NRT); Behavioral: Smartphone intervention with adherence components (ADHERE); Behavioral: Telephone Counseling

Varenicline + Smartphone Intervention without adherence (VAR + NO ADHERE)

EXPERIMENTAL

Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.

Drug: Varenicline (VAR); Behavioral: Smartphone intervention without adherence components (NO ADHERE); Behavioral: Telephone Counseling

Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + NO ADHERE)

EXPERIMENTAL

Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.

Drug: Varenicline (VAR); Drug: Nicotine lozenge (NRT); Behavioral: Smartphone intervention without adherence components (NO ADHERE); Behavioral: Telephone Counseling

Interventions

Varenicline (VAR) DRUG

13 weeks of varenicline

Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + ADHERE); Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + NO ADHERE); Varenicline + Smartphone Intervention with adherence components (VAR + ADHERE); Varenicline + Smartphone Intervention without adherence (VAR + NO ADHERE)

Nicotine lozenge (NRT) DRUG

12 weeks of nicotine lozenges

Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + ADHERE); Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + NO ADHERE)

Smartphone intervention without adherence components (NO ADHERE) BEHAVIORAL

Smartphone-based smoking cessation intervention without adherence components

Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + NO ADHERE); Varenicline + Smartphone Intervention without adherence (VAR + NO ADHERE)

Telephone Counseling BEHAVIORAL

Up to 6 telephone counseling sessions with a tobacco treatment specialist

Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + ADHERE); Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + NO ADHERE); Varenicline + Smartphone Intervention with adherence components (VAR + ADHERE); Varenicline + Smartphone Intervention without adherence (VAR + NO ADHERE)

Smartphone intervention with adherence components (ADHERE) BEHAVIORAL

Smartphone-based smoking cessation intervention with adherence components

Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + ADHERE); Varenicline + Smartphone Intervention with adherence components (VAR + ADHERE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide documentation of identity (to prevent fraudulent enrollment) and Oklahoma residence (due to limitations on prescribing to out-of-state residents)
• Reports daily smoking ≥5 cigarettes per day
• Provides a breath CO sample ≥6ppm to verify current smoking
• Willing to schedule a smoking cessation attempt within the next 1-2 weeks
• Willing to abstain from smoking cannabis or other combustible products during the study
• Willing to use varenicline and nicotine lozenges
• Willing to participate in the study for ≈6 months
• Able to demonstrate \>6th grade literacy which is necessary to read intervention materials and complete study assessments

You may not qualify if:

• History of seizures (varenicline contraindication)
• History of allergic reaction to varenicline
• Pregnant, planning to become pregnant, or currently breastfeeding
• Unwilling or unable to use varenicline or nicotine lozenges for other reasons (e.g., severe dry mouth, past history of severe medication side effects)
• Other medical reasons at the discretion of the prescribing physician (e.g., uncontrolled hypertension, recent myocardial infarction)
• Weekly or more frequent use of combustible cannabis during the past 30 days with a score ≥2 on the Cannabis Use Disorder Identification Test-Short Form

Sponsors & Collaborators

• University of Oklahoma: lead
• National Cancer Institute (NCI): collaborator
• Brown University: collaborator
• Thomas Jefferson University: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University: collaborator

Study Sites (1)

TSET Health Promotion Research Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Smoking Cessation; Medication Adherence

Interventions

Varenicline; Tobacco Use Cessation Devices; Nicotine Replacement Therapy

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Therapeutics; Drug Therapy

Study Officials

• Darla E. Kendzor, Ph.D.

  The University of Oklahoma Health Sciences

  PRINCIPAL INVESTIGATOR

• Jasjit S. Ahluwalia, MD

  Brown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannon Gwin, Ph.D.

CONTACT

(405) 271-8001; Shannon-Gwin@ouhsc.edu

Sharon Glassman

CONTACT

(405) 271-8001; Sharon-Glassman@ouhsc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will employ a 2x2 factorial design in which participants will be randomized to combinations of two treatment factors: 1) pharmacological treatment (varenicline + nicotine lozenges vs. varenicline alone) and 2) smartphone medication adherence intervention (smartphone-based smoking cessation app with vs. without adherence components). The primary study outcome will be biochemically confirmed 7-day point prevalence abstinence at 26 weeks after the scheduled quit date.

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 1, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)