Switching to E-cigarettes in Smokers Not Interested in Quitting

4th Generation E-cigarettes: Reducing Harm and Quitting Combustible Cigarettes in Dual Users

The objectives of this application are to 1) compare short- and long-term harm reduction and abuse liability potential of a nicotine salt pod-based electronic cigarettes (EC) in adult (AA) exclusive EC, dual cig-EC, and exclusive cig users, 2) characterize factors that predict who switches fully, partially, or not at all, and 3) examine if harm reduction can be further enhanced by treating dual users with varenicline (VAR) to eliminate cigarette smoking.

Study Overview

• Status: Recruiting
• Conditions: Smoking Reduction
• Intervention / Treatment: Drug: Varenicline Tartrate; Other: Electronic cigarette; Drug: Placebo

Detailed Description

Adult cigarette smokers (n=500) who are interested in switching to a nicotine salt-based electronic cigarette (EC) and are not established EC users will receive a 6-week supply of the EC and assistance with switching. After six weeks, those that are dual users (n=221) will receive an additional 12 weeks of the EC and be randomized in a 2:1 fashion to receive 12 weeks of varenicline (VAR) or placebo (PBO) and additional counseling to support a complete switch. Follow-up for all participants will continue through week 52. The primary outcome is change in the potent lung carcinogen, NNAL, between exclusive EC, dual cig-EC, and exclusive cig users at week 6.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tricia Snow, MPH; Phone Number: 816-398-8960; Email: psnow@kumc.edu

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64130
      • Recruiting
      • University of Kansas Medical Center
      • Contact: Tricia Snow, MPH; Phone Number: 816-398-8960; Email: psnow@kumc.edu
    • Kansas City, Missouri, United States, 64130
      • Recruiting
      • Swope Health Central
      • Contact: Tricia Snow; Phone Number: 816-599-5311; Email: psnow@kumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• ≥ 21 years of age
• Smoke >5 cigarettes per day
• Smoked cigarettes for > 6 months
• Verified smoker (CO > 5 ppm)
• Functioning telephone
• Interested in switching to EC
• Willing to take varenicline and complete all study visits

Exclusion Criteria:

• Interested in quitting smoking
• Use of smoking cessation pharmacotherapy in the month prior to enrollment
• Use of other tobacco products in past 30 days (i.e., cigarillos, cigars, hookah, smokeless tobacco, pipes)
• EC use on > 4 of the past 30 days
• Uncontrolled hypertension: BP > 180 (systolic) or > 105 (diastolic)
• Heart-related event in the past 30 days
• Medical contraindications to VAR: unstable cardiac condition (e.g., unstable angina or AMI) cardiac event, or stroke in the past 4 weeks; renal impairment; history of clinically significant allergic reactions; history of epilepsy or seizure disorder; hospitalized for psychiatric issue in past 30 days; active suicidal ideation
• Pregnant, contemplating getting pregnant, or breastfeeding
• Plans to move from Kansas City metro area during the treatment and follow-up phase
• Another household member enrolled in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Varenicline and electronic cigarette; At the end of the 6-week open label phase, dual users of cigarettes and e-cigarettes will receive 1mg varenicline to take twice daily for 12 weeks. They will also receive an additional 12 weeks of the nicotine salt-based pod system e-cigarette.	Drug: Varenicline Tartrate; 0.5 mg once daily for days 1-3, 0.5mg twice daily for days 4-7 and 1.0 mg twice daily from day 8 through week 12.; Other: Electronic cigarette; Nicotine salt pod based e-cigarette in 5% nicotine
Placebo Comparator: Placebo and electronic cigarette; At the end of the 6-week open label phase, dual users of cigarettes and e-cigarettes will receive placebo pills to take twice daily for 12 weeks. They will also receive an additional 12 weeks of the nicotine salt-based pod system e-cigarette.	Other: Electronic cigarette; Nicotine salt pod based e-cigarette in 5% nicotine; Drug: Placebo; One pill (white) once daily for days 1-3, one pill (white) twice daily for days 4-7 and one pill (blue) twice daily from day 8 through week 12.
Other: Open label electronic cigarette; All participants will receive an initial 6-week supply of the study electronic cigarette.	Other: Electronic cigarette; Nicotine salt pod based e-cigarette in 5% nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in toxicant exposure as measured by NNAL (4- (methylnitrosamino)-1-(3-pyridyl)-1-butanol) .	Reduction in toxicant exposure as measured by NNAL excretion from baseline to week 6.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carbon Monoxide (CO) verified 7-day point prevalence abstinence from cigarettes	CO verified 7-day point prevalence abstinence from cigarettes at week 12 post randomization.	Week 12 post randomization

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Nicole Nollen, PhD, University of Kanas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2023
• Primary Completion (Estimated): December 7, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Smoking; Health Behavior; Smoking Reduction; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Manufactured Materials; Technology, Industry, and Agriculture; Smoking Devices; Benzazepines; Quinoxalines; Varenicline; Electronic Nicotine Delivery Systems
• Other Study ID Numbers: STUDY00146887

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No