Varenicline + Nicotine Lozenges for Smoking Cessation

(COMBO II Trial)

Overseen By Sharon Glassman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Must be taking: Varenicline, Nicotine lozenges

Disqualifiers: Seizures, Allergic to varenicline, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

496 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

Darla E. Kendzor, Ph.D.

Principal Investigator

The University of Oklahoma Health Sciences

Jasjit S. Ahluwalia, MD

Principal Investigator

Brown University

Are You a Good Fit for This Trial?

This trial is for adults who smoke cigarettes daily and are interested in quitting. Participants must be willing to use a smartphone app to help with medication adherence and can't already be using cessation pharmacotherapy or behavioral treatment.

Inclusion Criteria

Provides a breath CO sample ≥6ppm to verify current smoking

Willing to abstain from smoking cannabis or other combustible products during the study

Willing to participate in the study for ≈6 months

Exclusion Criteria

History of allergic reaction to varenicline

Pregnant, planning to become pregnant, or currently breastfeeding

I cannot use varenicline or nicotine lozenges due to severe side effects or conditions like dry mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 13 weeks of varenicline and 12 weeks of nicotine lozenges, with a smartphone-based intervention and up to 6 telephone counseling sessions.

13 weeks

Remote assessments and interventions

Follow-up

Participants are monitored for smoking abstinence and medication adherence, with assessments at 26 weeks post-quit date.

13 weeks

Remote assessments

Long-term Follow-up

Participants' smoking abstinence is biochemically verified at 26 weeks post-quit date.

13 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine lozenge
• Varenicline

Trial Overview The study tests if combining Varenicline (a smoking cessation drug) with nicotine lozenges and a smartphone adherence intervention helps people quit smoking better than just Varenicline alone. It's a randomized trial where participants also get either an app that tracks medication taking or one without these features.

How Is the Trial Designed?

Group I: Varenicline + Smartphone Intervention without adherence (VAR + NO ADHERE) Experimental Treatment 3 Interventions

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.

Group II: Varenicline + Smartphone Intervention with adherence components (VAR + ADHERE) Experimental Treatment 3 Interventions

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.

Group III: Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + NO ADHERE) Experimental Treatment 4 Interventions

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.

Group IV: Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + ADHERE) Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Thomas Jefferson University

Collaborator

Trials

475

Recruited

189,000+

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborator

Trials

164

Recruited

10,900+

OU Health Stephenson Cancer Center

Collaborator