Synthetic Cooling Agents in Cigarettes for Cancer Prevention

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Disqualifiers: COVID-19, Psychiatric conditions, Cardiac event, Pregnancy, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how synthetic cooling agents in cigarettes affect smokers' perceptions, usage, and the potential harm of smoking. The researchers aim to determine if these agents, introduced as a replacement for menthol, alter the appeal or addictiveness of cigarettes and their impact on lung health. Participants will try cigarettes with menthol, without menthol, with synthetic cooling agents (a new type of additive), and their usual brand. The trial seeks established smokers who can avoid tobacco products for 12 hours before sessions and who read and speak English. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on smoking alternatives.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you must abstain from using tobacco products 12 hours before each lab session.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that synthetic cooling agents, such as WS-3 and WS-23, are used in some cigarettes to provide a cooling sensation without adding flavor, similar to menthol. Tests in e-cigarettes have found that these agents affect the product's appeal and user experience.

Regarding safety, studies have examined their effects on cells in the lab. Research indicates they might harm lung cells by increasing oxidative stress. However, extensive studies on their long-term safety in cigarettes are still lacking.

In summary, while synthetic cooling agents have been tested for their impact on user experience and have shown some effects on cells, information about their safety in humans remains limited. Ongoing research aims to better understand their impact. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial on synthetic cooling agents in cigarettes for cancer prevention because it could offer a new way to reduce the harmful effects of smoking. Unlike traditional menthol cigarettes, which use menthol to create a cooling sensation, this approach uses synthetic cooling agents. These agents might provide the same cooling effect without some of the potential health risks associated with menthol. This innovation could help minimize the damage caused by smoking while maintaining the sensory experience smokers are accustomed to.

What evidence suggests that this trial's treatments could be effective for cancer prevention?

This trial will compare different types of cigarettes, including those with synthetic cooling agents, menthol, and non-menthol cigarettes. Research has shown that synthetic cooling agents in cigarettes might change how smokers perceive and use them. These agents create a cooling sensation similar to menthol but without the taste. This cooling effect is known to increase nicotine addiction. Early findings suggest that these agents can make cigarettes more appealing, similar to menthol, which is linked to higher addiction rates. Evidence indicates that synthetic cooling agents are widely discussed in relation to e-cigarettes, showing significant public interest and potential impact on smoking habits. ^{2 6 7 8 9}

Who Is on the Research Team?

Alayna P. Tackett, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 21-29 who regularly smoke cigarettes and can read and speak English. They must be willing to give informed consent and avoid tobacco products for 12 hours before lab sessions. Smokers with recent COVID-19, heart issues, serious psychiatric conditions, pregnancy or breastfeeding, attempts to quit smoking, or recent lung diseases are excluded.

Inclusion Criteria

I am between 21 and 29 years old.

Established cigarette user

Willing to provide informed consent and abstain from using tobacco products 12 hours prior to the three lab sessions

Exclusion Criteria

Currently pregnant, planning to become pregnant, or breastfeeding

Self-reported unstable or significant psychiatric conditions

I have had a heart problem in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to use 1 of 3 cigarette conditions at 3 different study visits over 3 weeks

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Menthol Cigarette Smoking
• Non-menthol Cigarette Smoking
• Synthetic Cooling Agent Cigarette Smoking
• Usual Brand Cigarette Smoking

Trial Overview The study examines the effects of synthetic cooling agents in cigarettes on smokers' perceptions and usage compared to usual brands and menthol cigarettes. It involves spirometry tests (to measure lung function), questionnaires, and analysis of nasal lining fluids to assess respiratory impact.

How Is the Trial Designed?

Group I: Menthol cigarette Active Control 5 Interventions

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.

Group II: Non-menthol cigarette Active Control 5 Interventions

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.

Group III: Cigarette with synthetic cooling agents Active Control 5 Interventions

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.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Published Research Related to This Trial

Menthol cigarettes are particularly popular among younger smokers, with 56.7% of 12-17 year olds and 45.0% of 18-25 year olds using them, compared to lower rates in older age groups.

While overall smoking rates for non-menthol cigarettes decreased among adolescents and young adults from 2004 to 2010, menthol cigarette use remained constant or even increased, indicating that mentholated cigarettes may hinder efforts to reduce youth smoking rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential trends in cigarette smoking in the USA: is menthol slowing progress? Giovino, GA., Villanti, AC., Mowery, PD., et al.[2022]

Menthol, as a flavoring ingredient in cigarettes, does not significantly change the toxicity of cigarette smoke or the associated health risks of smoking, according to a review of scientific and epidemiological data up to mid-2009.

Further research is needed to understand how menthol may influence smoking behaviors such as initiation, cessation, and addiction, separate from other social and environmental factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review and assessment of menthol employed as a cigarette flavoring ingredient. Heck, JD.[2023]

Five large epidemiological studies found no evidence that smoking mentholated cigarettes increases the risk of lung cancer, even among African-American male smokers who predominantly use menthols.

Mentholation does not significantly affect smoking behavior or health metrics such as puff volume, heart rate, or nicotine absorption, suggesting that its toxicological effects on adult smokers are likely minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible effects on smokers of cigarette mentholation: a review of the evidence relating to key research questions. Werley, MS., Coggins, CR., Lee, PN.[2022]

Synthetic cooling agents WS-3 and WS-23 were found in a majority of US-marketed E-cigarettes, including popular brands like Puffbar, indicating widespread use beyond just menthol-flavored products.

The levels of these synthetic coolants may pose health risks, as the margin of exposure (MOE) calculations showed values below the safety threshold of 100 for most daily use scenarios, suggesting potential consumer exposure exceeding safety limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment. Jabba, SV., Erythropel, HC., Torres, DG., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-cigarette-smoking-related-carcinoma-10-2023-17d8d

Synthetic Cooling Agents in Cigarettes for Cancer Prevention This clinical trial evaluates the impact of synthetic cooling agents in combustible cigarettes on smoking perceptions and use. Menthol, a natural chemical, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11076411/

Effects of 'Ice' flavoured e-cigarettes with synthetic cooling ... This clinical experiment tested the effects of exposure to e-cigarettes with WS-23 or menthol cooling additives on user appeal and sensory attributes.

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.036106

Cardiovascular Health Effects and Synthetic Cooling ... Cardiovascular Health Effects and Synthetic Cooling Agents in E‐Cigarettes Labeled as “Clear” Marketed in Massachusetts After the Tobacco ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10557767/

Public perceptions of synthetic cooling agents in electronic ... This study examines public views on synthetic cooling agents in e-cigarettes via Twitter data. From May 2021 to March 2023, we used Twitter Streaming API.

5. kucancercenter.org kucancercenter.org/news-room/news/2022/04/study-to-gauge-effectiveness-of-menthol-e-cigarettes-as-a-quit-smoking-tool

Study to gauge effectiveness of menthol e-cigarettes as a ... Researchers at The University of Kansas Cancer Center have received a five-year, $3.9 million grant to explore the effectiveness of menthol- ...

6. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.036106?doi=10.1161/JAHA.124.036106

Cardiovascular Health Effects and Synthetic Cooling ... Chemical evaluation demonstrated the presence of synthetic cooling agents in “clear” e‐liquids along with menthol and additional flavor ...

7. trdrp.org trdrp.org/what-we-fund/research-priorities/cancer-health-disparities.html

Cancer health disparities The impact of menthol and/or non-menthol synthetic cooling agents (such as WS-3 and WS-23) on cellular processes such as proliferation, cell cycle checkpoint ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2214750022001792

The role of synthetic coolants, WS-3 and WS-23, in ... Coolants in e-cigarettes modify acellular and ROS levels in lung epithelial cells. •. Synthetic coolants in e-cigarette affect oxidative stress in lung cells.

9. dukecancerinstitute.org dukecancerinstitute.org/research-programs/cancer-prevention-and-control

Cancer Prevention and Control Dr. Jordt, in his lab, has examined synthetic cooling agents that mimic the effects of menthol in cigarettes both in terms of addictive properties and harm.