Menthol-Flavored E-Cigarettes for Smoking Cessation

Overseen By Tricia Snow

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nikki Nollen, PhD, MA

Must not be taking: Smoking cessation drugs

Disqualifiers: Pregnancy, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if menthol-flavored e-cigarettes help menthol cigarette smokers switch from regular cigarettes more effectively than tobacco-flavored e-cigarettes. Participants will receive either menthol or tobacco-flavored e-cigarettes for 12 weeks. The trial targets adults who have smoked menthol cigarettes daily for at least six months and are interested in trying e-cigarettes. As an unphased trial, it offers participants a unique opportunity to explore alternative smoking options and contribute to valuable research.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications, but you cannot use smoking cessation medications in the month before joining.

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

Research has shown that the FDA has approved menthol-flavored electronic cigarettes, indicating they have passed safety checks for specific uses. This approval suggests they are generally safe. E-cigarettes, in general, have been linked to higher success rates for quitting smoking compared to other methods.

The safety of tobacco-flavored e-cigarettes is less certain. E-cigarettes can expose users to risks of tobacco-related diseases. Some users have reported short-term health effects, but long-term data is insufficient to fully understand the risks.

Both types of e-cigarettes carry some risk, but menthol-flavored ones have more safety support from regulatory approvals. It is important to weigh the potential risks and benefits when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using menthol-flavored and tobacco-flavored electronic cigarettes for smoking cessation because these options could offer a more appealing and potentially less harmful alternative to traditional nicotine replacement therapies like patches or gum. Unlike these standard treatments, which can sometimes lack the sensory satisfaction of smoking, e-cigarettes mimic the hand-to-mouth action and provide a similar throat hit, making the transition away from smoking easier for some users. The flavors, particularly menthol, may also enhance the user experience, potentially increasing the likelihood of quitting smoking successfully. These features may help address both the physical and behavioral aspects of nicotine addiction, offering a novel approach to smoking cessation.

What evidence suggests that this trial's treatments could be effective for smoking cessation?

This trial will compare menthol-flavored electronic cigarettes with tobacco-flavored electronic cigarettes for smoking cessation. Research has shown that menthol-flavored e-cigarettes might help more people quit smoking than tobacco-flavored ones. One study found that people using menthol or mint-flavored e-cigarettes were more likely to stop smoking, with 9.2% of users quitting. Another study showed that menthol e-cigarettes reduced the urge to smoke more than tobacco-flavored ones. However, the effect of tobacco-flavored e-cigarettes remains less clear. Some reviews suggest that all e-cigarettes, regardless of flavor, can aid smoking cessation, but the evidence for tobacco flavor alone is not strong. Overall, menthol-flavored e-cigarettes seem to have a slight advantage in helping people quit smoking. ^{2 6 7 8 9}

Who Is on the Research Team?

Nicole Nollen, PhD

Principal Investigator

University of Kanas Medical Center

Are You a Good Fit for This Trial?

This trial is for adult menthol smokers who smoke at least 5 cigarettes daily, have been smoking menthol cigarettes for over 6 months, and are interested in switching to e-cigarettes. They must be over 21 with a functioning phone. People can't join if they've used e-cigarettes or smoking cessation aids recently, have uncontrolled high blood pressure, are pregnant/breastfeeding, plan to move away soon, or want to quit smoking.

Inclusion Criteria

Smoke ≥ 5 cigarettes per day (CPD)

Smoke menthol cigarettes for ≥ 6 months

Verified smoker (CO >5ppm)

Exclusion Criteria

Interested in quitting smoking

E-cigarette use on ≥ 4 of the past 30 days

Pregnant, contemplating getting pregnant, or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either menthol-flavored or tobacco-flavored e-cigarettes for 12 weeks

12 weeks

Regular visits for monitoring and supply of e-cigarettes

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 weeks

Periodic visits to assess switching and respiratory symptoms

What Are the Treatments Tested in This Trial?

Interventions

• Menthol-flavored electronic cigarette
• Tobacco-flavored electronic cigarette

Trial Overview The study is testing whether using menthol-flavored or tobacco-flavored nicotine salt-based pod-system e-cigarettes helps adult menthol smokers switch from regular cigarettes to e-cigarettes more effectively.

How Is the Trial Designed?

Group I: Menthol Flavor Electronic Cigarette Active Control 1 Intervention

400 adult cigarette smokers will receive 12 weeks of menthol-flavored electronic cigarettes.

Group II: Tobacco Flavor Electronic Cigarette Active Control 1 Intervention

400 adult cigarette smokers will receive 12 weeks of tobacco-flavored electronic cigarettes.

Menthol-flavored electronic cigarette is already approved in United States for the following indications:

Approved in United States as NJOY ACE Pod Menthol for:

• Adult smoking cessation aid

Who Is Running the Clinical Trial?

Nikki Nollen, PhD, MA

Lead Sponsor

Trials

3

Recruited

1,300+

Published Research Related to This Trial

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]

In studies with 17 and 19 cigarette smokers, e-cigarette flavors like cherry and menthol were found to enhance the perceived pleasantness and taste compared to tobacco and unflavored options, suggesting that flavor can influence user experience.

Modified risk messages, such as claims of reduced harm or carcinogen exposure, led to lower ratings of unpleasant effects from e-cigarettes, although they did not significantly change perceptions of harm, indicating that messaging may affect subjective experiences but not overall harm beliefs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Electronic Cigarette Liquid Flavors and Modified Risk Messages on Perceptions and Subjective Effects of E-Cigarettes. Bono, RS., Barnes, AJ., Lester, RC., 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]

Flavored e-liquids, specifically menthol and green apple, significantly increase the self-administration and reinforcement behaviors in male mice, indicating a higher likelihood of addiction-related behaviors associated with these flavors.

The study demonstrates that even zero-nicotine flavored e-liquids can be self-administered by mice, suggesting that flavors alone can drive vaping behavior, independent of nicotine content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flavors Enhance Nicotine Vapor Self-administration in Male Mice. Cooper, SY., Akers, AT., Henderson, BJ.[2021]

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]

Inhaled menthol from e-cigarettes did not enhance the positive effects of nicotine but significantly increased negative effects in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers.

Menthol-preferring smokers experienced blunted positive responses to nicotine and less severe withdrawal symptoms, potentially due to slower nicotine metabolism linked to chronic menthol exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers. Valentine, GW., DeVito, EE., Jatlow, PI., et al.[2020]

Menthol cigarette smokers had significantly lower quit rates compared to nonmenthol smokers, with only 13% of menthol smokers remaining abstinent at week 26 versus 30% of nonmenthol smokers, indicating that menthol use may hinder smoking cessation efforts.

Additionally, menthol smokers who successfully quit experienced greater weight gain (average of 14.87 lbs) compared to nonmenthol smokers (average of 7.95 lbs), suggesting that menthol cigarettes may complicate not only quitting but also the management of postcessation weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menthol cigarette use predicts treatment outcomes of weight-concerned smokers. Rojewski, AM., Toll, BA., O'Malley, SS.[2021]

In a six-week pilot study involving 47 menthol cigarette smokers, a total menthol ban (including e-cigarettes) led to increased cigarette consumption compared to a ban on menthol cigarettes alone, suggesting that including e-cigarettes in such bans may alter smoking behavior.

Participants in both menthol ban conditions reported lower cravings and less liking for cigarettes compared to those in the no ban group, indicating that menthol bans could potentially reduce the appeal of smoking, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on Tobacco Use and Subjective Measures of Including E-cigarettes in a Simulated Ban of Menthol in Combustible Cigarettes. Kotlyar, M., Shanley, R., Dufresne, SR., et al.[2023]

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 pilot study with 37 African American menthol smokers, those who abstained from menthol cigarettes for 8 weeks smoked significantly fewer cigarettes and had lower exhaled carbon monoxide levels compared to those who did not abstain.

Participants who abstained from menthol cigarettes reported greater motivation to quit and felt more effective in their quitting skills, suggesting that banning menthol in cigarettes could enhance the harm reduction potential of e-cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of restricting menthol flavored cigarettes or E-cigarettes on smoking behavior in menthol smokers. Kotlyar, M., Shanley, R., Dufresne, SR., et al.[2023]

In a study involving experienced smokers, menthol flavors in cigarette substitutes were found to be significantly more satisfying than a placebo, indicating that flavor plays a crucial role in the smoking experience.

Menthol smokers experienced a notable reduction in craving when using a menthol-flavored substitute, suggesting that flavor can enhance the effectiveness of smoking cessation aids for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of flavor in cigarette substitutes. Levin, ED., Behm, F., Rose, JE.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11294961/

E-Cigarette Characteristics and Cigarette Cessation ... Use of menthol or mint vs tobacco flavor e-cigarettes was associated with greater overall cigarette discontinuation rates (9.2% [95% CI, 6.6%- ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871624000310

Effects of mint, menthol, and tobacco-flavored e-cigarettes ... In this laboratory pilot study, mint and menthol (vs. tobacco) flavored e-cigarettes provided some negative reinforcement effects via acute reductions in ...

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Study to gauge effectiveness of menthol e-cigarettes as a ... “Our research has consistently shown that menthol cigarettes are more addictive and harder to quit,” Dr. Nollen said. “With this study we hope ...

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E-Cigarettes, Vapes, and other Electronic Nicotine Delivery ... To date, FDA has authorized 39 tobacco- and menthol-flavored e-cigarette products and devices. These products have undergone rigorous ...

5. keepitsacred.itcmi.org keepitsacred.itcmi.org/tobacco-and-tradition/commercial-tobacco/menthol-and-other-flavored-tobacco-products/

Menthol and Other Flavored Tobacco Products | Keep It Sacred Menthol and flavored tobacco has been recognized as a catalyst for smoking initiation and addiction, posing an additional hurdle to quitting efforts. AI/AN ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9910159/

Associations Between E-cigarette Use and ... E-cigarette use is positively associated with both making smoking quit attempts and quit success. Those using flavored e-cigarettes, particularly menthol or ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308815

Electronic Nicotine-Delivery Systems for Smoking Cessation The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772724623000136

The role of flavored electronic nicotine delivery systems in ... Persons regularly using menthol-flavored ENDS were no more likely to quit smoking than those regularly using tobacco-flavored ENDS. Three studies used the US ...

9. tobaccofreekids.org tobaccofreekids.org/us-resources/fact-sheet/electronic-cigarettes-an-overview-of-key-issues

Electronic Cigarettes: An Overview of Key Issues 110 A 2020 meta-analysis found that daily e-cigarette use was associated with increased smoking cessation while less than daily e-cigarette use was associated ...