The Abuse Liability of a Novel Heated Tobacco Product (IQOS) and Its Feasibility as a Menthol Cigarette Substitute

NCT ID: NCT05499377

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-28
• Study Completion Date: 2023-09-22

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.

Conditions

Tobacco Use

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Tobacco product administration and assessment

Intervention Type: DEVICE

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).

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

Group Type: EXPERIMENTAL

Tobacco product administration and assessment

Intervention Type: DEVICE

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).

Interventions

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).

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew J Barnes, PhD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

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 Aug 5;69(5):108029. doi: 10.1016/j.amepre.2025.108029. Online ahead of print.

Reference Type: DERIVED

PMID: 40763831 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1F30DA057047

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U54DA036105

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HM20024873

Identifier Type: -

Identifier Source: org_study_id