Tobacco Use
Conditions
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
Brief 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. 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.
Interventions
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).
Sponsors
National Institute on Drug Abuse (NIDA)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Average Daily Cigarette Use Per Day From Baseline | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cigarette Craving Suppression Questionnaire | Week 2, Friday Clinical Lab Visit (10 puff bout period) | 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 |
| Puff Topography (Puff Duration) | Week 2, Friday Clinical Lab visit (10 puff bout period) | 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. |
| Average Daily IQOS Usage | Week 2 (intervention week), Tuesday-Thursday | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tobacco-Flavored IQOS Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System
Tobacco product administration and assessment: 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). | 12 |
| Menthol-Flavored IQOS Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System
Tobacco product administration and assessment: 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). | 18 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Tobacco-Flavored IQOS | Menthol-Flavored IQOS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 18 Participants | 29 Participants |
| Age, Continuous | 46.1 years STANDARD_DEVIATION 12.6 | 43.0 years STANDARD_DEVIATION 8.3 | 44.2 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 15 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 13 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 8 Participants |
| Region of Enrollment United States | 12 Participants | 18 Participants | 30 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 18 |
| other Total, other adverse events | 0 / 12 | 0 / 18 |
| serious Total, serious adverse events | 0 / 12 | 0 / 18 |
Outcome results
Primary
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.
Time frame: Week 1 (baseline) to Week 2 (intervention)
Population: Percent change in Average Daily Cigarette Use per day from baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobacco-Flavored IQOS | Percent Change in Average Daily Cigarette Use Per Day From Baseline | 36.8 % reduction in cigarettes per day |
| Menthol-Flavored IQOS | Percent Change in Average Daily Cigarette Use Per Day From Baseline | 80.36 % reduction in cigarettes per day |
Primary
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).
Time frame: Week 2, Friday Clinical Lab visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tobacco-Flavored IQOS | Percent Increase in Demand as the Subject is Willing to Substitute From Cigarettes to HTPs Using the Experimental Tobacco Marketplace Task | 0.14 percent increase in demand/dollars | Standard Deviation 0.4 |
| Menthol-Flavored IQOS | Percent Increase in Demand as the Subject is Willing to Substitute From Cigarettes to HTPs Using the Experimental Tobacco Marketplace Task | 0.67 percent increase in demand/dollars | Standard Deviation 0.8 |
Primary
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.
Time frame: Week 2, Friday Clinical Lab visit (10 puff bout period)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobacco-Flavored IQOS | Plasma Nicotine Delivery | 6.3 Nicotine boost (ng/mL) |
| Menthol-Flavored IQOS | Plasma Nicotine Delivery | 6.6 Nicotine boost (ng/mL) |
Secondary
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.
Time frame: Week 2 (intervention week), Tuesday-Thursday
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tobacco-Flavored IQOS | Average Daily IQOS Usage | 4.5 IQOS sticks per day |
| Menthol-Flavored IQOS | Average Daily IQOS Usage | 4.3 IQOS sticks per day |
Secondary
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
Time frame: Week 2, Friday Clinical Lab Visit (10 puff bout period)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobacco-Flavored IQOS | Cigarette Craving Suppression Questionnaire | -9.5 change in craving (0-100) scale |
| Menthol-Flavored IQOS | Cigarette Craving Suppression Questionnaire | -41.5 change in craving (0-100) scale |
Secondary
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.
Time frame: Week 2, Friday Clinical Lab visit (10 puff bout period)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobacco-Flavored IQOS | Puff Topography (Puff Duration) | 1.64 seconds |
| Menthol-Flavored IQOS | Puff Topography (Puff Duration) | 1.33 seconds |