Tobacco UseNCT05499377
The Abuse Liability of a Novel Heated Tobacco Product (IQOS) and Its Feasibility as a Menthol Cigarette Substitute
A study testing Tobacco product administration and assessment in people with Tobacco Use, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
This project examines the influence of flavor availability on switching to an MRTP known as IQOS, part of the Heated Tobacco Product (HTP) class, among menthol smokers using clinical lab and naturalistic evaluations of abuse liability. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tobacco Use
- What is being tested?
- Tobacco product administration and assessment
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2022to 22 Sep 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy adults (aged 21 and older)
- Daily menthol cigarette smokers
- Exhaled Carbon Monoxide (CO) reading of > 5 PPM at in-person screening (to confirm smoking status)
- A 'positive' cotinine cassette result to verify nicotine use at the in-person screening.
- Participants must be willing to provide informed consent and abstain from nicotine/tobacco for ≥8 hours prior to each lab session.
- Participants must have access to a computer/smartphone and be willing to receive and respond to daily surveys
- Able to read and write in English
Who cannot join
- Daily use of any tobacco products other than cigarettes
- Self-reported history of chronic medical or psychiatric conditions
- Women will be excluded if they test positive for pregnancy (by urinalysis) or self-report breastfeeding.
- Some details of the study inclusion and exclusion criteria are omitted at this time, to preserve scientific integrity. Full inclusion and exclusion criteria will be posted following study completion.
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Effects of Heated Tobacco Product Flavor on Tobacco Use Behavior and Abuse Liability Among Menthol Cigarette Smokers
This project examines the influence of flavor availability on switching to an MRTP known as IQOS, part of the Heated Tobacco Product (HTP) class, among menthol smokers using clinical lab and naturalistic evaluations of abuse liability. Results will help federal regulators predict the public health impact on menthol cigarette smokers of policies restricting access to menthol-flavored HTPs.
Read the detailed description
The public health success of FDA's proposed ban on menthol cigarettes hinges upon whether menthol smokers who are unable to quit smoking switch to non-menthol cigarettes (no public health gain) or to potentially lower harm alternatives like heated tobacco products (HTP). In 2019, FDA authorized an HTP called "IQOS" and its tobacco- and menthol-flavored "HeatSticks" (HS) as a modified risk tobacco product (MRTP). One issue relevant to FDA's future action regarding IQOS will be "whether and how certain flavors may help adult cigarette smokers reduce cigarette use and switch to potentially less harmful products" (FDA, 2018). Understanding the potential for HTPs like IQOS to reduce the health burden of cigarettes requires targeted research investigating the extent to which flavor availability is important for menthol smokers to switch to HTPs. For one tobacco product to substitute for another, their abuse liabilities should be congruent. Validated clinical lab methods exist for comparing tobacco product abuse liability by characterizing their nicotine delivery profiles (via plasma nicotine and puff topography) and reinforcing efficacy (via subjective and behavioral measures). Naturalistic assessment can validate clinical lab results regarding use patterns and product substitution.
The current study involves a two-arm, two-week, parallel group trial. The first week is an own brand (OB) menthol cigarette baseline, during which tobacco use will be assessed daily using ecological momentary assessment (EMA). On Monday and Friday, participants will complete clinical lab sessions that involve using OB cigarettes and responding to subjective measures and an Experimental Tobacco Marketplace (ETM) task that assesses willingness to substitute menthol cigarettes with an array of tobacco products including IQOS. During the next week, participants will be randomized to receive IQOS-menthol (n=25) or IQOS-tobacco (n=25); EMA and clinical lab visits will be repeated. Aim 1 assesses IQOS' abuse liability in a clinical lab setting. Outcomes include plasma nicotine levels, puffing behavior, responses about subjective effects, and product substitution from the ETM task. Aim 2 measures tobacco use patterns in naturalistic settings where participants will report daily OB and IQOS use outcomes via EMA. The overarching hypothesis is that, relative to OB, IQOS-menthol's abuse liability profile will differ less than IQOS-tobacco's, suggesting that menthol smokers will be more likely to substitute an HTP for combustible menthol cigarettes when a menthol-flavored HTP is available. Results will deepen our understanding of the public health impact of HTPs and policies that might restrict access to menthol-flavored MRTPs.
- Conditions
- Tobacco Use
- Being tested
- Tobacco product administration and assessment
- Keywords
- Heated Tobacco Products, Flavor, Abuse Liability, Tobacco, Cigarettes, Menthol, Experimental Tobacco Marketplace, Nicotine Delivery, Puff Topography, Ecological Momentary Assessment, Modified Risk Tobacco Product, IQOS, Heated Tobacco Products Flavors
- Medical subject headings
- Tobacco Use
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobacco product administration and assessmentDevice
Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
| Study group | Role | What they receive |
|---|---|---|
| Tobacco-Flavored IQOS | Active comparator | Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Receives: Device: Tobacco product administration and assessment |
| Menthol-Flavored IQOS | Experimental | Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Receives: Device: Tobacco product administration and assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Average Daily Cigarette Use Per Day From Baseline
Average number of cigarettes consumed per day, collected via daily text/email survey, averaged overconsumption for Tues-Thurs of each week. Outcome will compare the percent change in cigarette consumption from the baseline week (OB menthol cigarette use) to the intervention week (IQOS use) between the two study arms.
Measured: Week 1 (baseline) to Week 2 (intervention)
Percent Increase in Demand as the Subject is Willing to Substitute From Cigarettes to HTPs Using the Experimental Tobacco Marketplace Task
Participants will complete the Experimental Tobacco Marketplace Task - which asks participants to allocate a hypothetical budget across a large menu of products. In each session, cigarette prices increased ($0.12, $0.25, $0.50, $1.00. and $2.00 per cigarette) while prices for alternative products remained fixed. Across three ETM sessions, either all products, all products except little cigars and cigarillos (LCCs), or all products except ENDS (JUUL e-cigarettes) were available. Linear regression is performed on individual participant data using log-transformed cigarette price to determine demand and substitution. Reported demand for tobacco products is used to determine substitution between IQOS and cigarettes. Purchasing decisions are not reinforced. Outcome will compare the cross-price elasticity (CPE) of IQOS with respect to menthol cigarettes among those with access to IQOS-menthol and IQOS-Tobacco (IQOS-M group) compared to those with access to IQOS-tobacco only (IQOS-T group).
Measured: Week 2, Friday Clinical Lab visit
Plasma Nicotine Delivery
Change in the plasma nicotine levels from before to after a standardized 10-puff (30-sec interpuff interval) bout with IQOS in the participant's assigned flavor. Outcome will compare the average plasma nicotine boost (the change in plasma nicotine levels from before to after the standardized puffing bout) across two study arms as well as compared to own-brand menthol cigarettes.
Measured: Week 2, Friday Clinical Lab visit (10 puff bout period)
Secondary outcomes (3)
Cigarette Craving Suppression Questionnaire
We will compare the degree of "cigarette craving" will be assessed before and after a 10-puff use bout of IQOS. Cigarette craving will be assessed before and after a standardized puffing bout using the Questionnaire of Smoking Urges (QSU), which features 7-point likert-like scales. The reduction in "urges to smoke" item from the QSU will be used in this assessment. The average cigarette craving suppression score will be compared across the two experimental IQOS groups. The Tobacco Craving Questionnaire (TCQ) is a valid and reliable 47-item self-report instrument that assesses tobacco craving in four dimensions: emotionality, expectancy, compulsivity, and purposefulness. The higher your score, the more likely you are to have withdrawal symptoms if you give up smoking; also, the withdrawal symptoms are likely to be stronger
Measured: Week 2, Friday Clinical Lab Visit (10 puff bout period)
Puff Topography (Puff Duration)
Average duration per puff during a standardized 10-puff (30-sec interpuff interval) bout with IQOS in assigned flavor. Puff duration will be measured using a validated puff topography instrument that attaches to the IQOS device. Outcome will compare the average puff duration across two study arms.
Measured: Week 2, Friday Clinical Lab visit (10 puff bout period)
Average Daily IQOS Usage
Number of IQOS HeatSticks used each day will be assessed during the study. We will compare the number of Heatsticks used per day, on average (from Tues-Thurs of intervention week), between the two study arms.
Measured: Week 2 (intervention week), Tuesday-Thursday
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2022
- Study start28 Nov 2022
- Primary completion22 Sep 2023
- Study completion22 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tobacco UseStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Andrew J Barnes, PhD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05499377
- Sponsor's protocol ID
- HM20024873
- Other IDs
- 1F30DA057047, U54DA036105
- Status last verified
- Jan 2025
- First submitted
- 10 Aug 2022
- Last updated
- 31 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
White AM, Imran R, Gaitan N, Bickel WK, Perera RA, Cobb CO, Eissenberg TE, Barnes AJ. A Pilot RCT Exploring Heated Tobacco Product Substitution for Menthol Cigarettes. Am J Prev Med. 2025 Nov;69(5):108029. doi: 10.1016/j.amepre.2025.108029. Epub 2025 Aug 5.
PubMed 40763831
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Heated Tobacco Product Flavor on Tobacco Use Behavior and Abuse Liability Among Menthol Cigarette Smokers
- ClinicalTrials.gov ID
- NCT05499377
- Acronym / sponsor ID
- HM20024873
- Conditions
- Tobacco Use
- Keywords
- Heated Tobacco Products, Flavor, Abuse Liability, Tobacco, Cigarettes, Menthol, Experimental Tobacco Marketplace, Nicotine Delivery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 28 Nov 2022 (actual)
- Primary completion
- 22 Sep 2023 (actual)
- Study completion
- 22 Sep 2023 (actual)
- First posted
- 12 Aug 2022 (actual)
- Results
- Posted 31 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project examines the influence of flavor availability on switching to an MRTP known as IQOS, part of the Heated Tobacco Product (HTP) class, among menthol smokers using clinical lab and naturalistic evaluations of abuse liability. Results will help federal regulators predict the public health impact on menthol cigarette smokers of policies restricting access to menthol-flavored HTPs.
Detailed description
The public health success of FDA's proposed ban on menthol cigarettes hinges upon whether menthol smokers who are unable to quit smoking switch to non-menthol cigarettes (no public health gain) or to potentially lower harm alternatives like heated tobacco products (HTP). In 2019, FDA authorized an HTP called "IQOS" and its tobacco- and menthol-flavored "HeatSticks" (HS) as a modified risk tobacco product (MRTP). One issue relevant to FDA's future action regarding IQOS will be "whether and how certain flavors may help adult cigarette smokers reduce cigarette use and switch to potentially less harmful products" (FDA, 2018). Understanding the potential for HTPs like IQOS to reduce the health burden of cigarettes requires targeted research investigating the extent to which flavor availability is important for menthol smokers to switch to HTPs. For one tobacco product to substitute for another, their abuse liabilities should be congruent. Validated clinical lab methods exist for comparing tobacco product abuse liability by characterizing their nicotine delivery profiles (via plasma nicotine and puff topography) and reinforcing efficacy (via subjective and behavioral measures). Naturalistic assessment can validate clinical lab results regarding use patterns and product substitution.
The current study involves a two-arm, two-week, parallel group trial. The first week is an own brand (OB) menthol cigarette baseline, during which tobacco use will be assessed daily using ecological momentary assessment (EMA). On Monday and Friday, participants will complete clinical lab sessions that involve using OB cigarettes and responding to subjective measures and an Experimental Tobacco Marketplace (ETM) task that assesses willingness to substitute menthol cigarettes with an array of tobacco products including IQOS. During the next week, participants will be randomized to receive IQOS-menthol (n=25) or IQOS-tobacco (n=25); EMA and clinical lab visits will be repeated. Aim 1 assesses IQOS' abuse liability in a clinical lab setting. Outcomes include plasma nicotine levels, puffing behavior, responses about subjective effects, and product substitution from the ETM task. Aim 2 measures tobacco use patterns in naturalistic settings where participants will report daily OB and IQOS use outcomes via EMA. The overarching hypothesis is that, relative to OB, IQOS-menthol's abuse liability profile will differ less than IQOS-tobacco's, suggesting that menthol smokers will be more likely to substitute an HTP for combustible menthol cigarettes when a menthol-flavored HTP is available. Results will deepen our understanding of the public health impact of HTPs and policies that might restrict access to menthol-flavored MRTPs.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tobacco-Flavored IQOS | Active comparator | Device: Tobacco product administration and assessmentTobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System |
| Menthol-Flavored IQOS | Experimental | Device: Tobacco product administration and assessmentMenthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy adults (aged 21 and older)
- Daily menthol cigarette smokers
- Exhaled Carbon Monoxide (CO) reading of > 5 PPM at in-person screening (to confirm smoking status)
- A 'positive' cotinine cassette result to verify nicotine use at the in-person screening.
- Participants must be willing to provide informed consent and abstain from nicotine/tobacco for ≥8 hours prior to each lab session.
Key exclusion criteria (4 listed)
- Daily use of any tobacco products other than cigarettes
- Self-reported history of chronic medical or psychiatric conditions
- Women will be excluded if they test positive for pregnancy (by urinalysis) or self-report breastfeeding.
- Some details of the study inclusion and exclusion criteria are omitted at this time, to preserve scientific integrity. Full inclusion and exclusion criteria will be posted following study completion.
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 |
|---|---|---|
| Tobacco product administration and assessmentParticipants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week). | Device | Menthol-Flavored IQOS, Tobacco-Flavored IQOS |
Primary outcome
Percent Change in Average Daily Cigarette Use Per Day From Baseline
Time frame: Week 1 (baseline) to Week 2 (intervention)
Average number of cigarettes consumed per day, collected via daily text/email survey, averaged overconsumption for Tues-Thurs of each week. Outcome will compare the percent change in cigarette consumption from the baseline week (OB menthol cigarette use) to the intervention week (IQOS use) between the two study arms.
Percent Increase in Demand as the Subject is Willing to Substitute From Cigarettes to HTPs Using the Experimental Tobacco Marketplace Task
Time frame: Week 2, Friday Clinical Lab visit
Participants will complete the Experimental Tobacco Marketplace Task - which asks participants to allocate a hypothetical budget across a large menu of products. In each session, cigarette prices increased ($0.12, $0.25, $0.50, $1.00. and $2.00 per cigarette) while prices for alternative products remained fixed. Across three ETM sessions, either all products, all products except little cigars and cigarillos (LCCs), or all products except ENDS (JUUL e-cigarettes) were available. Linear regression is performed on individual participant data using log-transformed cigarette price to determine demand and substitution. Reported demand for tobacco products is used to determine substitution between IQOS and cigarettes. Purchasing decisions are not reinforced. Outcome will compare the cross-price elasticity (CPE) of IQOS with respect to menthol cigarettes among those with access to IQOS-menthol and IQOS-Tobacco (IQOS-M group) compared to those with access to IQOS-tobacco only (IQOS-T group).
Plasma Nicotine Delivery
Time frame: Week 2, Friday Clinical Lab visit (10 puff bout period)
Change in the plasma nicotine levels from before to after a standardized 10-puff (30-sec interpuff interval) bout with IQOS in the participant's assigned flavor. Outcome will compare the average plasma nicotine boost (the change in plasma nicotine levels from before to after the standardized puffing bout) across two study arms as well as compared to own-brand menthol cigarettes.
3 secondary outcomes
Cigarette Craving Suppression Questionnaire
Time frame: Week 2, Friday Clinical Lab Visit (10 puff bout period)
Puff Topography (Puff Duration)
Time frame: Week 2, Friday Clinical Lab visit (10 puff bout period)
Average Daily IQOS Usage
Time frame: Week 2 (intervention week), Tuesday-Thursday
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40763831White AM, Imran R, Gaitan N, Bickel WK, Perera RA, Cobb CO, Eissenberg TE, Barnes AJ. A Pilot RCT Exploring Heated Tobacco Product Substitution for Menthol Cigarettes. Am J Prev Med. 2025 Nov;69(5):108029. doi: 10.1016/j.amepre.2025.108029. Epub 2025 Aug 5.
- 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. This study is not recruiting at the moment.
Andrew J Barnes, PhD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tobacco product administration and assessment in people with Tobacco Use, run by Virginia Commonwealth University 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 7 inclusion and 4 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: finished, as of the sponsor's last update on 31 Jan 2025. 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?
Yes. Results are posted in the registry (first posted 31 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Average Daily Cigarette Use Per Day From Baseline (time frame: Week 1 (baseline) to Week 2 (intervention)). The study lists 3 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 NCT05499377, 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 31 Jan 2025.