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

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

Interventions

DRUG

Varenicline (VAR)

13 weeks of varenicline

DRUG

Nicotine lozenge (NRT)

12 weeks of nicotine lozenges

BEHAVIORAL

Smartphone intervention with adherence components (ADHERE)

Smartphone-based smoking cessation intervention with adherence components

BEHAVIORAL

Smartphone intervention without adherence components (NO ADHERE)

Smartphone-based smoking cessation intervention without adherence components

BEHAVIORAL

Telephone Counseling

Up to 6 telephone counseling sessions with a tobacco treatment specialist

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Brown University

  collaborator OTHER

• Thomas Jefferson University

  collaborator OTHER

• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  collaborator OTHER

• University of Oklahoma

  lead OTHER

Principal Investigators

• Darla E. Kendzor, Ph.D. · The University of Oklahoma Health Sciences

• Jasjit S. Ahluwalia, MD · Brown University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-05-31

Primary Completion

2029-06-01

Completion

2029-06-01

FDA Drug

Yes

Countries

• United States

Study Locations