SmokingNCT06264154
The Role of Flavor in the Substitutability of E-cigarettes for Combustible Cigarettes Among Persistent Smokers
A study testing E-cigarettes in people with Smoking and Tobacco Use, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This between-subjects study aims to evaluate the effect of flavor on initial and sustained switching from combustible cigarettes to e-cigarettes among 210 cigarette smokers. After measuring baseline cigarette smoking rate, participants will be randomized to a six-week regimen of fruit-flavored, tobacco-flavored, or… Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Smoking, Tobacco Use, Cigarette Smoking
- What is being tested?
- E-cigarettes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2024to Dec 2027
- Phase
- Interventional
- 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
- Able to communicate fluently in English (i.e. speaking, writing, and reading)
- Male and female smokers who are > 21 years of age and self-report smoking at least 5 cigarettes (menthol and/or non-menthol) per day for at least the last 12 months
- 5 or more failed quit attempts and the use of smoking cessation medication on at least one prior attempt.
- Ever use of an e-cigarette
- Have a carbon monoxide (CO) greater than 10 ppm
- Not using any forms of nicotine regularly other than cigarettes
Show all 9Show fewer
- Be willing to switch to e-cigarettes for 6 weeks and use the assigned flavors
- Plan to live in the area for the duration of the study
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.
Who cannot join
- Smoking Behavior Regular use of nicotine-containing products other than cigarettes (e.g., chewing tobacco, snuff, snus, cigars, e-cigs, etc.). Regular e-cigarette use is defined as greater than 5 days/past 30 days
- Participants agreeing to abstain from using nicotine-containing products other than cigarettes for the duration of the study will be considered eligible.
- Current enrollment or plans to enroll in a smoking cessation program over the duration of the study.
- Current use of smoking cessation medication
- Provide a CO breath test reading less than 10 ppm at Intake.
- Alcohol and Drug
Show all 20Show fewer
- History of substance abuse (other than nicotine dependence) in the past 12 months.
- Current alcohol consumption that exceeds 20 standard drinks/week.
- Current use of recreational drugs (other than nicotine and cannabis)
- Breath alcohol reading (BrAC) greater than .000 at Intake.
- Medical
- Women, including all individuals assigned as "female" at birth, who are pregnant, breastfeeding, or planning a pregnancy over the duration of the study period.
- Serious or unstable disease within the past year (e.g. cancer, heart disease). Applicable conditions will be evaluated on a case-by-case basis by the Principal Investigator.
- Allergies to either propylene glycol or flavor additives
- Psychiatric
- 1. Lifetime history of schizophrenia or psychosis.
- General Exclusion
- Past, current, anticipated, or pending enrollment in another research program over the study period that could potentially impact subject safety, study data, and/or the study design as determined by the Principal Investigator.
- Any medical condition, illness, disorder, adverse event (AE), or concomitant medication that could compromise participant safety or significantly impact study performance as determined by the Principal Investigator. Subjects may be deemed ineligible for any of the aforementioned reasons at any point throughout the study, as well as during the initial telephone screen.
- Significant non-compliance with protocol and/or study design as determined by the Principal Investigator and/o. Subjects may be deemed ineligible at any point throughout the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Janet Audrain-McGovern, Ph.D., 215-746-7145, audrain@pennmedicine.upenn.edu
About this study
This between-subjects study aims to evaluate the effect of flavor on initial and sustained switching from combustible cigarettes to e-cigarettes among 210 cigarette smokers. After measuring baseline cigarette smoking rate, participants will be randomized to a six-week regimen of fruit-flavored, tobacco-flavored, or menthol-flavored e-cigarettes and be instructed to switch (versus smoking cigarettes) over a 6-week period. Flavor-associated subjective reward and the reinforcing value of flavored e-cigarettes relative to combustible cigarettes will be assessed as mechanisms.
Read the detailed description
The average smoker will attempt to quit smoking at least 30 times before abstaining for 12 months or longer. These attempts typically occur over decades of smoking, carcinogen and toxicant exposure, resulting in 480,000 deaths annually. As highlighted in the Surgeon General's Report, helping smokers who cannot quit smoking switch to less harmful non-combustible nicotine-containing products, such as e-cigarettes, has the potential to reduce this health burden dramatically. Substituting e-cigarettes for combustible cigarettes might only be possible for persistent smokers if e-cigarettes are accessible and appealing. Harm reduction proponents have advocated for the continued availability of e-cigarette flavors to appeal to and aid cigarette smokers unable to quit with traditional methods. Yet, there are no prospective studies of the effect of flavor on initial and sustained switching from combustible to electronic cigarettes. Converging laboratory, epidemiological, and clinical research suggests that fruit-flavored e-cigarettes with nicotine may be a viable substitute for combustible cigarettes among persistent smokers. The proposed study seeks to answer two novel questions relevant to public health and the regulation of e-cigarette flavoring. First, do persistent smokers substitute fruit-flavored e- cigarettes more readily than traditional-flavored e-cigarettes (tobacco or menthol) for combustible cigarettes? Second, are fruit-flavored e-cigarettes more rewarding and reinforcing than traditional-flavored e-cigarettes, and do these effects facilitate switching? The proposed research will fill these gaps in the evidence base by randomizing 210 persistent cigarette smokers to a six-week regimen of fruit-flavored (FF: watermelon and blueberry, n=70), tobacco-flavored (TF n=70) or menthol-flavored (MF n=70) e-cigarettes in a between-subjects design. Baseline smoking rate will be established during days 1-5. After biochemically verified overnight cigarette smoking abstinence, laboratory visits on days 6 and 7 will assess flavor-associated subjective reward and the reinforcing value of flavored e-cigarettes relative to combustible cigarettes. Participants will then switch from cigarette smoking to e-cigarette use for six weeks. Participants will collect spent cigarette filters daily to assess cigarettes smoked per day (cpd) if they smoke. The primary outcome measure is the longitudinal daily count of cigarettes from baseline to the end of the six-week switch period, with cigarettes per day at a 6-month follow-up as a secondary endpoint.
- Conditions
- Smoking, Tobacco Use, Cigarette Smoking, E-Cig Use
- Being tested
- E-cigarettes
- Medical subject headings
- Smoking, Tobacco Use, Cigarette Smoking, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E-cigarettesOther
All participants are instructed to switch from smoking combustible cigarettes to using e-cigarettes for 6 weeks. Participants will receive an e-cigarette device and flavored nicotine pods according to their randomly assigned flavor.
| Study group | Role | What they receive |
|---|---|---|
| Fruit-flavored E-cigarettes | Experimental | Participants randomized to fruit-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and fruit-flavored nicotine pods. Participants will be able to choose between blueberry or watermelon-flavored pods. They will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior. Receives: Other: E-cigarettes |
| Tobacco-flavored E-cigarettes | Active comparator | Participants randomized to tobacco-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and tobacco nicotine pods. Participants will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior. Receives: Other: E-cigarettes |
| Menthol-flavored E-cigarettes | Active comparator | Participants randomized to menthol-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and menthol nicotine pods. Participants will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior. Receives: Other: E-cigarettes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cigarette Consumption
The primary outcome is the longitudinal daily count of cigarettes from baseline to the end of the e-cigarette switch phase. Daily cigarette consumption will be determined by counting the daily spent cigarette filters returned for each of the 42 days (days 8 - 49).
Measured: 42 days (days 8 - 49)
Cigarette Smoking Behavior
Cigarette smoking behavior at the 6-month follow-up will serve as a secondary endpoint.
Measured: 19 Weeks (Day 50-6-Month Follow-Up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start26 Aug 2024
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SmokingStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), University of Pennsylvania
- Responsible party
- Principal investigator, Janet E. Audrain-McGovern, PhD, University of Pennsylvania
- Investigators
- Janet Audrain-McGovern, Ph.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06264154
- Sponsor's protocol ID
- UPCC 11023
- Other IDs
- R01CA287474-01, 854051
- Status last verified
- Feb 2026
- First submitted
- 8 Feb 2024
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Klapec O, Strasser AA, Paul Wileyto E, Audrain-McGovern J. Evaluating the substitutability of fruit versus menthol and tobacco-flavored e-cigarettes on combustible cigarette cessation: Randomized clinical trial protocol. Contemp Clin Trials Commun. 2026 Jun 6;51:101652. doi: 10.1016/j.conctc.2026.101652. eCollection 2026 Jun.
PubMed 42293363
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Flavor in the Substitutability of E-cigarettes for Combustible Cigarettes Among Persistent Smokers
- ClinicalTrials.gov ID
- NCT06264154
- Acronym / sponsor ID
- UPCC 11023
- Conditions
- Smoking, Tobacco Use, Cigarette Smoking, E-Cig Use
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), University of Pennsylvania
- Study start
- 26 Aug 2024 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 16 Feb 2024 (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.
This between-subjects study aims to evaluate the effect of flavor on initial and sustained switching from combustible cigarettes to e-cigarettes among 210 cigarette smokers. After measuring baseline cigarette smoking rate, participants will be randomized to a six-week regimen of fruit-flavored, tobacco-flavored, or menthol-flavored e-cigarettes and be instructed to switch (versus smoking cigarettes) over a 6-week period. Flavor-associated subjective reward and the reinforcing value of flavored e-cigarettes relative to combustible cigarettes will be assessed as mechanisms.
Detailed description
The average smoker will attempt to quit smoking at least 30 times before abstaining for 12 months or longer. These attempts typically occur over decades of smoking, carcinogen and toxicant exposure, resulting in 480,000 deaths annually. As highlighted in the Surgeon General's Report, helping smokers who cannot quit smoking switch to less harmful non-combustible nicotine-containing products, such as e-cigarettes, has the potential to reduce this health burden dramatically. Substituting e-cigarettes for combustible cigarettes might only be possible for persistent smokers if e-cigarettes are accessible and appealing. Harm reduction proponents have advocated for the continued availability of e-cigarette flavors to appeal to and aid cigarette smokers unable to quit with traditional methods. Yet, there are no prospective studies of the effect of flavor on initial and sustained switching from combustible to electronic cigarettes. Converging laboratory, epidemiological, and clinical research suggests that fruit-flavored e-cigarettes with nicotine may be a viable substitute for combustible cigarettes among persistent smokers. The proposed study seeks to answer two novel questions relevant to public health and the regulation of e-cigarette flavoring. First, do persistent smokers substitute fruit-flavored e- cigarettes more readily than traditional-flavored e-cigarettes (tobacco or menthol) for combustible cigarettes? Second, are fruit-flavored e-cigarettes more rewarding and reinforcing than traditional-flavored e-cigarettes, and do these effects facilitate switching? The proposed research will fill these gaps in the evidence base by randomizing 210 persistent cigarette smokers to a six-week regimen of fruit-flavored (FF: watermelon and blueberry, n=70), tobacco-flavored (TF n=70) or menthol-flavored (MF n=70) e-cigarettes in a between-subjects design. Baseline smoking rate will be established during days 1-5. After biochemically verified overnight cigarette smoking abstinence, laboratory visits on days 6 and 7 will assess flavor-associated subjective reward and the reinforcing value of flavored e-cigarettes relative to combustible cigarettes. Participants will then switch from cigarette smoking to e-cigarette use for six weeks. Participants will collect spent cigarette filters daily to assess cigarettes smoked per day (cpd) if they smoke. The primary outcome measure is the longitudinal daily count of cigarettes from baseline to the end of the six-week switch period, with cigarettes per day at a 6-month follow-up as a secondary endpoint.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fruit-flavored E-cigarettes | Experimental | Other: E-cigarettesParticipants randomized to fruit-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and fruit-flavored nicotine pods. Participants will be able to choose between blueberry or watermelon-flavored pods. They will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior. |
| Tobacco-flavored E-cigarettes | Active comparator | Other: E-cigarettesParticipants randomized to tobacco-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and tobacco nicotine pods. Participants will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior. |
| Menthol-flavored E-cigarettes | Active comparator | Other: E-cigarettesParticipants randomized to menthol-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and menthol nicotine pods. Participants will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Able to communicate fluently in English (i.e. speaking, writing, and reading)
- Male and female smokers who are > 21 years of age and self-report smoking at least 5 cigarettes (menthol and/or non-menthol) per day for at least the last 12 months
- 5 or more failed quit attempts and the use of smoking cessation medication on at least one prior attempt.
- Ever use of an e-cigarette
- Have a carbon monoxide (CO) greater than 10 ppm
Key exclusion criteria (20 listed)
- Smoking Behavior Regular use of nicotine-containing products other than cigarettes (e.g., chewing tobacco, snuff, snus, cigars, e-cigs, etc.). Regular e-cigarette use is defined as greater than 5 days/past 30 days
- Participants agreeing to abstain from using nicotine-containing products other than cigarettes for the duration of the study will be considered eligible.
- Current enrollment or plans to enroll in a smoking cessation program over the duration of the study.
- Current use of smoking cessation medication
- Provide a CO breath test reading less than 10 ppm at Intake.
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 |
|---|---|---|
| E-cigarettesAll participants are instructed to switch from smoking combustible cigarettes to using e-cigarettes for 6 weeks. Participants will receive an e-cigarette device and flavored nicotine pods according to their randomly assigned flavor. | Other | Fruit-flavored E-cigarettes, Menthol-flavored E-cigarettes, Tobacco-flavored E-cigarettes |
Primary outcome
Cigarette Consumption
Time frame: 42 days (days 8 - 49)
The primary outcome is the longitudinal daily count of cigarettes from baseline to the end of the e-cigarette switch phase. Daily cigarette consumption will be determined by counting the daily spent cigarette filters returned for each of the 42 days (days 8 - 49).
Cigarette Smoking Behavior
Time frame: 19 Weeks (Day 50-6-Month Follow-Up)
Cigarette smoking behavior at the 6-month follow-up will serve as a secondary endpoint.
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 19 Feb 2026.
- Derived from this study: PubMed 42293363Klapec O, Strasser AA, Paul Wileyto E, Audrain-McGovern J. Evaluating the substitutability of fruit versus menthol and tobacco-flavored e-cigarettes on combustible cigarette cessation: Randomized clinical trial protocol. Contemp Clin Trials Commun. 2026 Jun 6;51:101652. doi: 10.1016/j.conctc.2026.101652. eCollection 2026 Jun.
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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.
Janet Audrain-McGovern, Ph.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing E-cigarettes in people with Smoking and Tobacco Use, run by Abramson Cancer Center at Penn Medicine at 1 site 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 9 inclusion and 20 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 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Janet Audrain-McGovern, Ph.D. ((215) 746-7145, audrain@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cigarette Consumption (time frame: 42 days (days 8 - 49)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06264154, which also lists 1 linked publication.
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 19 Feb 2026.