Menthol-Flavored E-Cigarettes for Vaping

Overseen By Wasim Maziak, PhD, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Florida International University

Must not be taking: Prescription medications

Disqualifiers: Chronic disease, Cardiovascular disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 sessions

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The use of electronic nicotine delivery systems (ENDS; e-cigarettes) has reached epidemic levels among young people in the United States (US). ENDS heat and vaporize a nicotine-containing liquid to produce an inhalable aerosol mist. While generally considered less harmful than combustible cigarettes, ENDS use exposes users to dependence-producing nicotine and respiratory and cardiovascular toxicants such as aldehydes. Flavor is a major factor in getting young people to use ENDS, thus limiting flavors to menthol and tobacco for prefilled cartridge ENDS "pod mods" was the first major action taken by the FDA to reduce the spread of ENDS among young people. Menthol flavor, however, can present a potential risk given its increasing popularity among young people in the US, and its puffing and nicotine-enhancing properties. Yet, the extent of menthol's ability to affect users' experience and puffing patterns, and how these affect dependence, exposure to toxicants, and clinical outcomes continue to be understudied. Such evidence will be critical to the FDA's ability to set further regulatory standards to reduce ENDS potential harm. The investigators will conduct a 2x2 (pre-post x menthol vs. tobacco flavor) crossover clinical lab study. The investigator will recruit current/past month ENDS users (n=250, 21-35 yrs), who will attend two sessions and use their ENDS once with menthol and once with tobacco flavors. The proposed studies will answer two key regulatory questions consistent with FDA's focus on the role of flavor in tobacco products' addiction and toxicity; 1) compared to tobacco flavor, does menthol carry additional risk by enhancing puffing, abuse liability, and toxicant exposure in ENDS users, and; 2) is this effect more pronounced among high dependence compared to other users. Other outcomes such as harm perception, satisfaction, clinical responses, intention to use or quit, and group comparisons such as according to race, and sex will allow the FDA a comprehensive assessment of the pros and cons of regulating mentholated ENDS for different segments of the society. Such evidence will help advance FDA regulatory policies with the potential to reduce ENDS harm.

Will I have to stop taking my current medications?

The trial excludes individuals who regularly use prescription medications (other than vitamins or birth control), so you may need to stop taking your current medications to participate.

What data supports the effectiveness of menthol-flavored e-cigarettes as a treatment?

Menthol-flavored e-cigarettes and other cooling flavors are popular among youth and may encourage smokers to switch from traditional cigarettes to e-cigarettes, potentially reducing harm from smoking. ^{1 2 3 4 5}

Is there any safety information available for menthol-flavored e-cigarettes?

The available research does not provide specific safety information about menthol-flavored e-cigarettes. Most studies focus on marketing, usage patterns, and regulatory impacts rather than direct safety assessments. ^{4 5 6 7 8}

How is the menthol-flavored e-cigarette treatment different from other treatments for vaping?

Menthol-flavored e-cigarettes are unique because they provide a cooling sensation that enhances their appeal, especially among youth, and may encourage the transition from traditional smoking to vaping. Unlike other treatments, they use menthol and synthetic cooling agents to create a pleasant sensory experience without the characteristic minty odor. ^{2 3 4 5 7}

Research Team

Wasim Maziak, PhD, MD

Principal Investigator

Florida International University

Eligibility Criteria

This trial is for healthy adults aged 21-35 who use e-cigarettes at least occasionally in the past month. Participants must not be pregnant, breastfeeding, or using other tobacco products regularly. They should have no chronic diseases, psychiatric conditions, cardiovascular issues, or regular medication use (except vitamins/birth control).

Inclusion Criteria

Generally healthy individuals (determined by physical examination)

Generally healthy individuals (determined by physical examination).

You have used e-cigarettes at least once in the past 30 days.

Exclusion Criteria

I am currently experiencing symptoms like cough, fever, or chest pain.

I am not pregnant or breastfeeding.

You have a long-term health condition or mental health condition that you have previously reported.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants attend two lab sessions to use menthol and tobacco-flavored e-cigarettes for up to 60 minutes each

2 sessions

2 visits (in-person)

Follow-up

Participants are monitored for changes in nicotine levels, respiratory function, and other clinical outcomes

4 weeks

Treatment Details

Interventions

• Menthol-flavored e-cigarette
• Tobacco-flavored e-cigarette

Trial Overview The study examines if menthol flavor in e-cigarettes affects addiction and exposure to toxicants more than tobacco flavor. It's a crossover study where participants will try both flavors during separate sessions and researchers will measure their puffing patterns and clinical responses.

Participant Groups

Group I: Tobacco-flavored e-cigarette Experimental Treatment 1 Intervention

All participants will complete a lab visit where they will use tobacco-flavored e-cigarette ad libitum for up to 60 minutes.

Group II: Menthol-flavored e-cigarette Experimental Treatment 1 Intervention

All participants will complete a lab visit where they will use menthol-flavored e-cigarette ad libitum for up to 60 minutes.

Menthol-flavored e-cigarette is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Menthol e-liquid for:

• None (regulated as a tobacco product)

Approved in European Union as Menthol e-liquid for:

• None (regulated as a tobacco product)

Approved in Canada as Menthol e-liquid for:

• None (regulated as a tobacco product)

Approved in Japan as Menthol e-liquid for:

• None (regulated as a tobacco product)

Approved in China as Menthol e-liquid for:

• None (regulated as a tobacco product)

Who Is Running the Clinical Trial?

Florida International University

Lead Sponsor

Trials

114

Recruited

19,400+

Findings from Research

Menthol smokers using JUUL were more likely to switch from cigarettes to vaping compared to nonmenthol smokers, with 42.6% of menthol smokers switching versus 38.8% of nonmenthol smokers, indicating a potential advantage of ENDS for this group.

A significant preference for Menthol/Mint-flavored JUULpods was observed among menthol smokers (53.8%) compared to nonmenthol smokers (22.9%), suggesting that offering menthol-flavored ENDS could enhance switching rates among menthol smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System. Goldenson, NI., Augustson, EM., Shiffman, S.[2022]

A study analyzing over 14,000 e-liquid products from five online vape shops found that fruit flavors were the most popular, followed by dessert and candy flavors, indicating a strong preference among youth users for sweet and fruity options.

The findings suggest that many e-liquids are marketed with multiple flavor profiles, which may complicate regulatory efforts by the FDA to restrict certain flavors, highlighting the need for further investigation into compliance with flavor restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the E-Liquid Flavor Wheel: Classification of Emerging E-Liquid Flavors in Online Vape Shops. Ma, S., Qiu, Z., Yang, Q., et al.[2023]

From January 2017 to November 2021, sales of cooling flavoured e-cigarettes in the USA surged by 693%, indicating a growing popularity among consumers, particularly youth.

The proportion of non-menthol cooling disposable e-cigarettes skyrocketed, highlighting a shift in consumer preference away from traditional menthol flavours, which could impact future regulatory strategies for flavoured e-cigarette use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in unit sales of cooling flavoured e-cigarettes, USA, 2017-2021. Ali, FRM., Seaman, EL., Diaz, MC., et al.[2022]

A study of 38 vape shop websites in the Greater Los Angeles Area identified 1330 e-liquid flavors, with 219 categorized as menthol, mint, or ice flavors, indicating a significant presence of cooling flavors in the market.

The majority of these cooling flavors (70.3% of ice flavors and 63.3% of menthol flavors) were marketed in combination with fruit, suggesting a trend towards appealing flavor profiles that may attract a wide range of consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A content analysis of website marketing for cooling flavored e-liquids in a sample of brick-and-mortar vape shops in the Greater Los Angeles area. Brown, N., Shin, H., Whooley, S., et al.[2022]

In a survey of 4,875 high school students, over half (51.6%) reported using e-cigarettes with cooling flavors, indicating a significant trend among youth.

The use of cooling flavors was linked to more frequent vaping and a higher likelihood of using nicotine, suggesting that these flavors may enhance the appeal and usage of e-cigarettes among young users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cooling e-cigarette flavors and the association with e-cigarette use among a sample of high school students. Davis, DR., Morean, ME., Bold, KW., et al.[2023]

In a study of 64 black and Latinx menthol cigarette smokers, both menthol and non-menthol e-cigarettes showed similar high rates of switching and acceptability, indicating that restricting menthol e-liquids may not negatively impact these smokers' transition to e-cigarettes.

Participants using menthol e-cigarettes reported comparable reductions in daily cigarette consumption and similar subjective effects to those using non-menthol e-cigarettes, suggesting that both types of e-cigarettes are effective alternatives for menthol smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menthol versus non-menthol flavouring and switching to e-cigarettes in black and Latinx adult menthol combustible cigarette smokers: secondary analyses from a randomised clinical trial. Nollen, NL., Leavens, ELS., Ahluwalia, JS., et al.[2023]

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]

Exclusive menthol cigarette use is significantly higher among non-Hispanic Black individuals and low-income adults compared to non-Hispanic White and high-income groups, indicating potential disparities in tobacco product preferences.

Younger adults are more likely to use sweet/spicy flavored e-cigarettes and combine different flavors with menthol cigarettes, suggesting that regulations targeting menthol cigarettes may need to include restrictions on appealing e-cigarette flavors to effectively reduce usage among this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flavoring Patterns of Exclusive and Dual-Use of Cigarettes and E-Cigarettes Among US Adults: Results from the TUS-CPS 2018-2019. Zavala-Arciniega, L., Hirschtick, JL., Meza, R., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Expanding the E-Liquid Flavor Wheel: Classification of Emerging E-Liquid Flavors in Online Vape Shops. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Trends in unit sales of cooling flavoured e-cigarettes, USA, 2017-2021. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

A content analysis of website marketing for cooling flavored e-liquids in a sample of brick-and-mortar vape shops in the Greater Los Angeles area. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Cooling e-cigarette flavors and the association with e-cigarette use among a sample of high school students. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Menthol versus non-menthol flavouring and switching to e-cigarettes in black and Latinx adult menthol combustible cigarette smokers: secondary analyses from a randomised clinical trial. [2023]

7. England 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Flavoring Patterns of Exclusive and Dual-Use of Cigarettes and E-Cigarettes Among US Adults: Results from the TUS-CPS 2018-2019. [2023]