Smoking ReductionPhase 3NCT05703672
Switching to E-cigarettes in Smokers Not Interested in Quitting
A Phase 3 study testing Varenicline Tartrate and Electronic cigarette in people with Smoking Reduction, run by University of Kansas Medical Center at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Smoking Reduction
- What is being tested?
- Varenicline Tartrate and Electronic cigarette
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jul 2023to 28 Feb 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ≥ 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Swope Health Central
Kansas City, Missouri, 64130
Tricia Snow, 816-599-5311, psnow@kumc.edu
- Recruiting
University of Kansas Medical Center
Kansas City, Missouri, 64130
Tricia Snow, MPH, 816-398-8960, psnow@kumc.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Smoking Reduction
- Being tested
- Varenicline Tartrate, Placebo, Electronic cigarette
- Medical subject headings
- Smoking Reduction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Varenicline TartrateDrug
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.
PlaceboDrug
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.
Electronic cigaretteOther
Nicotine salt pod based e-cigarette in 5% nicotine
| Study group | Role | What they receive |
|---|---|---|
| Varenicline and electronic cigarette | Experimental | 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. Receives: Drug: Varenicline Tartrate; Other: Electronic cigarette |
| Placebo and electronic cigarette | Placebo comparator | 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. Receives: Drug: Placebo; Other: Electronic cigarette |
| Open label electronic cigarette | Other | All participants will receive an initial 6-week supply of the study electronic cigarette. Receives: Other: Electronic cigarette |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 6
Secondary outcomes (1)
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.
Measured: Week 12 post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start17 Jul 2023
- Primary completion7 Dec 2026 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoking ReductionStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicole Nollen, PhD, Principal investigator, University of Kanas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05703672
- Sponsor's protocol ID
- STUDY00146887
- Status last verified
- Oct 2026
- First submitted
- 19 Jan 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 4th Generation E-cigarettes: Reducing Harm and Quitting Combustible Cigarettes in Dual Users
- ClinicalTrials.gov ID
- NCT05703672
- Acronym / sponsor ID
- STUDY00146887
- Conditions
- Smoking Reduction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 17 Jul 2023 (actual)
- Primary completion
- 7 Dec 2026 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Varenicline and electronic cigarette | Experimental | Drug: Varenicline Tartrate, Other: Electronic cigaretteAt 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. |
| Placebo and electronic cigarette | Placebo comparator | Drug: Placebo, Other: Electronic cigaretteAt 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. |
| Open label electronic cigarette | Other | Other: Electronic cigaretteAll participants will receive an initial 6-week supply of the study electronic cigarette. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥ 21 years of age
- Smoke >5 cigarettes per day
- Smoked cigarettes for > 6 months
- Verified smoker (CO > 5 ppm)
- Functioning telephone
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Varenicline Tartrate0.5 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. | Drug | Varenicline and electronic cigarette |
| PlaceboOne 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. | Drug | Placebo and electronic cigarette |
| Electronic cigaretteNicotine salt pod based e-cigarette in 5% nicotine | Other | Open label electronic cigarette, Placebo and electronic cigarette, Varenicline and electronic cigarette |
Primary outcome
Reduction in toxicant exposure as measured by NNAL (4- (methylnitrosamino)-1-(3-pyridyl)-1-butanol) .
Time frame: Week 6
Reduction in toxicant exposure as measured by NNAL excretion from baseline to week 6.
1 secondary outcome
Carbon Monoxide (CO) verified 7-day point prevalence abstinence from cigarettes
Time frame: Week 12 post randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicole Nollen, PhD principal investigator
University of Kanas Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Varenicline Tartrate and Electronic cigarette in people with Smoking Reduction, run by University of Kansas Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tricia Snow, MPH (816-398-8960, psnow@kumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in toxicant exposure as measured by NNAL (4- (methylnitrosamino)-1-(3-pyridyl)-1-butanol) . (time frame: Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.