Evaluating the Impact of Synthetic Cooling Agents in Combustible Cigarettes on Smoking Perceptions and Use

Synthetic Cooling Agents in Combustible Cigarettes: A Pilot Study

This clinical trial evaluates the impact of synthetic cooling agents in combustible cigarettes on smoking perceptions and use. Menthol, a natural chemical, is a cooling agent that increases nicotine dependence among smokers. Menthol cigarettes largely contribute to the huge burden that smoking puts on public health. Approximately 43% of adult smokers smoke menthol cigarettes. Regulatory agencies have begun a ban on menthol. In response to the ban, the tobacco industry has introduced synthetic cooling agents as a flavorless replacement to provide the same cooling effects as menthol. Information gained from this trial may help researchers determine how the addition of synthetic cooling agents changes the appeal, abuse liability potential, and respiratory toxicity profile of combustible cigarettes.

Study Overview

• Status: Completed
• Conditions: Cigarette Smoking-Related Carcinoma
• Intervention / Treatment: Diagnostic test: Spirometry; Behavioral: Menthol Cigarette Smoking; Behavioral: Usual Brand Cigarette Smoking; Other: Questionnaire Administration; Diagnostic test: Nasal Epithelial Lining Fluid; Behavioral: Non-menthol Cigarette Smoking; Behavioral: Synthetic Cooling Agent Cigarette Smoking

Detailed Description

PRIMARY OBJECTIVES:

I. Assess the content of synthetic cooling agents in newly introduced cooling agent non-menthol, menthol, and traditional non-menthol cigarettes.

II. Assess the subjective effects and abuse liability of cooling agent non-menthol cigarettes.

EXPLORATORY OBJECTIVE:

I. Examine acute changes to pulmonary health associated with cooling agent cigarette use.

OUTLINE: Participants are randomized to use 1 of 3 cigarette conditions at 3 different study visits.

Participants participate in ad libitum smoking sessions with either a non-menthol control, menthol, or synthetic cooling agent cigarette condition once weekly (QW) over 3 weeks on study. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the study cigarette condition at the end of each study visit. Participants also undergo nasal swab collection over 5-10 minutes and spirometry and airwave oscillometry testing over 5-10 minutes pre- and post-smoking session at each study visit.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 21 - 29 years
• Established cigarette user
• Willing to provide informed consent and abstain from using tobacco products 12 hours prior to the three lab sessions
• Read and speak English

Exclusion Criteria:

• Recently coronavirus disease 2019 positive (COVID-19+) or a recent COVID-19 hospitalization
• Self-reported unstable or significant psychiatric conditions
• History of cardiac event or distress within the past 3 months
• Are currently pregnant, planning to become pregnant, or breastfeeding
• Currently attempting to quit using combustible tobacco products
• Have suffered from any serious lung disease or infection in the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Menthol cigarette; Participants participate in an ad libitum smoking session with a menthol cigarette for this condition. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the menthol study cigarette at the end of each study visit.	Diagnostic test: Spirometry; Pulmonary function test; Behavioral: Menthol Cigarette Smoking; Smoke a menthol cigarette; Behavioral: Usual Brand Cigarette Smoking; Smoke usual brand cigarette; Other: Questionnaire Administration; Survey questionnaires; Diagnostic test: Nasal Epithelial Lining Fluid; Nasal strip inserted into the nare to collect nasal epithelial lining fluid.
Active Comparator: Non-menthol cigarette; Participants participate in an ad libitum smoking session with a non-menthol control cigarette for this condition. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the non-menthol study cigarette at the end of each study visit.	Diagnostic test: Spirometry; Pulmonary function test; Behavioral: Usual Brand Cigarette Smoking; Smoke usual brand cigarette; Other: Questionnaire Administration; Survey questionnaires; Diagnostic test: Nasal Epithelial Lining Fluid; Nasal strip inserted into the nare to collect nasal epithelial lining fluid.; Behavioral: Non-menthol Cigarette Smoking; Smoke a non-menthol cigarette
Active Comparator: Cigarette with synthetic cooling agents; Participants participate in an ad libitum smoking session with a synthetic cooling agent cigarette for this condition. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the synthetic cooling agent study cigarette at the end of each study visit.	Diagnostic test: Spirometry; Pulmonary function test; Behavioral: Usual Brand Cigarette Smoking; Smoke usual brand cigarette; Other: Questionnaire Administration; Survey questionnaires; Diagnostic test: Nasal Epithelial Lining Fluid; Nasal strip inserted into the nare to collect nasal epithelial lining fluid.; Behavioral: Synthetic Cooling Agent Cigarette Smoking; Smoke a synthetic cooling agent cigarette

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cigarette Chemical Contents	Before participant recruitment began, chemical content analysis of 3 cigarettes of each study condition was performed. We used liquid-liquid extraction (LLE) to extract nicotine, WS-3, WS-23, and menthol from cigarette samples and quantified these analytes using gas chromatography-mass spectrometry (GC-MS).	Approximately 3 months prior to start of participant recruitment
Impact of Cooling Effects on Demand Via the Forced Choice Task	At each study visit, after the participant has smoked the study cigarette, the participant must choose between smoking the study cigarette again, or smoking one of their own, usual brand cigarettes. Within each arm, the proportion of participants who opt to continue smoking the study cigarette will be reported. This will measure if demand for the study cigarettes is great enough to overcome the desire for the participant's own preferred cigarettes.	After completion of study cigarette smoking session (Week 1, Week 2, Week 3)
Abuse Liability Via Puff Topography - Total Smoking Time	Will be measured with a topography device that records frequency, duration, and flow rate of cigarette puffs. These measures are combined to inform overall cigarette puff behavior. Greater frequency, duration, and flow rate of cigarette puffs suggest greater abuse liability.	During study cigarette smoking session (Week 1, Week 2, Week 3)
Abuse Liability Via Puff Topography - Average Puff Duration	Will be measured with a topography device that records frequency, duration, and flow rate of cigarette puffs. These measures are combined to inform overall cigarette puff behavior. Greater frequency, duration, and flow rate of cigarette puffs suggest greater abuse liability.	During study cigarette smoking session (Week 1, Week 2, Week 3)
Abuse Liability Via Puff Topography - Average Flow Rate	Will be measured with a topography device that records frequency, duration, and flow rate of cigarette puffs. These measures are combined to inform overall cigarette puff behavior. Greater frequency, duration, and flow rate of cigarette puffs suggest greater abuse liability.	During study cigarette smoking session (Week 1, Week 2, Week 3)
Abuse Liability Via Puff Topography - Average Inter-Puff Interval	Will be measured with a topography device that records frequency, duration, and flow rate of cigarette puffs. These measures are combined to inform overall cigarette puff behavior. Greater frequency, duration, and flow rate of cigarette puffs suggest greater abuse liability.	During study cigarette smoking session (Week 1, Week 2, Week 3)
Abuse Liability Via Puff Topography - Average Puff Volume	Will be measured with a topography device that records frequency, duration, and flow rate of cigarette puffs. These measures are combined to inform overall cigarette puff behavior. Greater frequency, duration, and flow rate of cigarette puffs suggest greater abuse liability.	During study cigarette smoking session (Week 1, Week 2, Week 3)
Cigarette Appeal	Participants will complete the Appeal and Sensory Quality questionnaire after smoking each study cigarette. This questionnaire will ask participants to rate each study cigarette for appeal characteristics such as liking, willingness to use again, flavor intensity, pleasantness of taste, etc. on a scale of 0 (not at all)-100(extremely). Higher scores indicate greater liking, willingness to use again, flavor intensity, etc.	Post study cigarette smoking session (Week1, Week 2, Week 3)

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Alayna P Tackett, PhD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2023
• Primary Completion (Actual): June 12, 2024
• Study Completion (Actual): June 12, 2024

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Respiratory System; Respiratory Function Tests; Spirometry
• Other Study ID Numbers: OSU-23208; NCI-2023-10761 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes