Effects of Tobacco Flavoring and Liquid Composition on Vaping Topography for Tobacco-Related Cancer

Overseen By Richard O'Connor

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Roswell Park Cancer Institute

Must not be taking: Nasal sprays, antihistamines

Disqualifiers: Pregnancy, COVID-19, allergies, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 7 sessions over 3 months

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial tests the effect of tobacco flavor and liquid composition on the way a person puffs on a vape (topography). In general, tobacco products are designed with sensory factors in mind, such as flavor, to increase the appeal. Flavors and the composition of nicotine, either made in a lab (synthetic) or from tobacco, may create positive sensory effects, such as look, feel and taste, and influence smoking behavior and willingness to try different types of cigarettes. Understanding how nicotine vaping products are used is important in assessing individual and population level health risks. Vape flavors and synthetic nicotine may be related to harmful effects on health from vaping and may impact the appeal, risk beliefs and vaping topography.

Will I have to stop taking my current medications?

The trial requires that you do not take medications known to interfere with taste or smell, such as certain nasal sprays, nasal antihistamines, decongestants, antibiotics, and medications containing zinc.

What data supports the effectiveness of this treatment for tobacco-related cancer?

The research suggests that electronic nicotine delivery systems (ENDS), like e-cigarettes, might help reduce smoking rates and the harmful effects of smoking, which could be beneficial for tobacco-related cancer prevention. However, more research is needed to fully understand their health impacts and effectiveness in smoking cessation. ^{1 2 3 4 5}

Is vaping generally safe for humans?

Research shows that e-cigarette aerosols contain harmful chemicals and metals that can cause respiratory problems. Some substances, like chromium and nickel, have been linked to higher cancer risks, indicating potential safety concerns with vaping. ^{1 2 4 6 7}

How does vaping differ from other treatments for tobacco-related cancer?

Vaping, or using e-cigarettes, is unique because it involves inhaling vaporized e-liquids, which can contain nicotine and various flavorings, as opposed to traditional treatments that might involve medication or surgery. It is primarily used as a harm reduction tool to help smokers transition away from traditional cigarettes, potentially reducing exposure to harmful chemicals found in cigarette smoke. ^{2 7 8 9 10}

Research Team

Richard O'Connor

Principal Investigator

Roswell Park

Eligibility Criteria

This trial is for daily vapers of nicotine products who don't use other tobacco items and consider themselves in good health. Women able to have children must test negative for pregnancy. Participants need to understand the study's experimental aspect and sign a consent form.

Inclusion Criteria

Current daily vapers of products containing nicotine

No daily concurrent use of other tobacco products

I consider myself to be in good health overall.

Exclusion Criteria

Active untreated seasonal allergies that would interfere with smell or taste procedures

I have noticed changes in my taste or smell.

Pregnant or nursing female participants

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo vaping sessions with different tobacco flavor and nicotine formulations, including saliva and optional oral cell and rinse sample collections

7 sessions over 3 months

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Biospecimen Collection
• Questionnaire Administration
• Vaping

Trial Overview The study examines how tobacco flavoring and liquid composition, including lab-made or natural nicotine, affect vaping habits (topography). It aims to understand the impact on appeal, risk perception, and usage patterns which are crucial for assessing health risks.

Participant Groups

Group I: Vaping - Experimental Treatment 3 Interventions

Description The order of directed and ad libitum bouts are randomized within participants at each session. SESSION 1: Participants puff their own brand liquid on study. SESSIONS 2-5: Participants puff 1 of 4 randomly assigned tobacco flavor formulations at each visit on study. SESSIONS 6-7: Participants puff 1 of 2 randomly assigned nicotine formulations at each visit on study. Participants also undergo collection of saliva samples and optionally undergo collection of oral cell and oral rinse samples throughout study.

Vaping is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as E-Cigarettes for:

• Nicotine replacement therapy for smoking cessation

Approved in United States as Electronic Nicotine Delivery Systems (ENDS) for:

• Nicotine replacement therapy for smoking cessation

Approved in Canada as Vaporizers for:

• Nicotine replacement therapy for smoking cessation

Approved in Japan as E-Liquids for:

• Nicotine replacement therapy for smoking cessation

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Over 1.5 years, there was a significant increase (156.4%) in the use of disposable devices with salt nicotine and no adjustable settings among frequent ENDS users, while the use of disposable pod/cartridges decreased by 15.2%.

Participants who switched from tank devices (which use freebase nicotine and have adjustable settings) to other device/liquid groupings reported higher nicotine concentrations and lower device power, indicating a trend towards stronger nicotine delivery with less powerful devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transitions in device and liquid characteristic groupings among US adults frequently using electronic nicotine delivery systems (ENDS) over three timepoints, 2020-2021. Nian, Q., Hardesty, JJ., Crespi, E., et al.[2023]

A study of 1,179 adult ENDS users revealed that 87% of users favored five specific combinations of devices and liquids, with the most common being reusable devices with adjustable settings and a free-base nicotine liquid at 5.2 mg/mL.

The second most popular combination involved reusable devices with no adjustable settings and nicotine salt liquids in disposable pods at a much higher concentration of 49.4 mg/mL, highlighting significant variability in nicotine exposure among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinations of electronic nicotine delivery system device and liquid characteristics among U.S. adults. Cohen, JE., Hardesty, JJ., Nian, Q., et al.[2022]

Electronic nicotine delivery systems (ENDS), like e-cigarettes, were introduced as a safer alternative for smokers, but their use has expanded to young people and non-smokers, raising concerns about unintended health risks.

The design and power of ENDS devices can significantly affect their safety, with higher power devices potentially being more hazardous, highlighting the need for ongoing research to understand the benefits and risks associated with these products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clearing the Haze: What Do We Still Need to Learn about Electronic Nicotine Delivery Systems? Fucito, LM., Malinosky, H., Baldassarri, SR., et al.[2023]

In a study of 1,489 adult ENDS users, sweet flavors were the most popular, making up 76.2% of the flavors used, while menthol/mint and tobacco flavors were significantly less common.

Users of sweet-flavored liquids tended to use lower nicotine concentrations and higher wattages, suggesting that flavor choice influences device settings and potentially user behavior, which has important implications for regulatory policies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device and liquid characteristics used with sweet, menthol/mint, and tobacco ENDS liquid flavors: The population-based VAPER study. Crespi, E., Hardesty, JJ., Nian, Q., et al.[2023]

Electronic nicotine delivery systems (ENDS), like e-cigarettes, have rapidly increased in use among both adults and youth, raising concerns about their potential to either help reduce smoking rates or inadvertently encourage tobacco use among non-smokers and former smokers.

The American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) emphasize the need for more research on ENDS to understand their health impacts and recommend strict regulations, including childproof packaging and prohibiting youth-targeted marketing, to mitigate potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: a policy statement from the American Association for Cancer Research and the American Society of Clinical Oncology. Brandon, TH., Goniewicz, ML., Hanna, NH., et al.[2022]

In 2018, an estimated 885 cases of liquid nicotine poisoning among children under 5 were treated in U.S. emergency departments, indicating a concerning trend in exposure.

The majority of these poisoning cases (90%) were treated and released, with ingestion being the most common route of exposure (99.4%), highlighting the need for increased public awareness and safety measures regarding liquid nicotine products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery system (ENDS) liquid nicotine exposure in young children presenting to US emergency departments, 2018. Chang, JT., Rostron, BL.[2022]

This study analyzed the aerosol from popular disposable e-cigarettes, Puff Bar and Air Bar, revealing harmful organic chemicals and metals that can lead to respiratory issues.

The estimated cancer risks from chromium and nickel in the e-cigarette aerosols were significantly higher than acceptable levels, highlighting serious health concerns associated with ENDS use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disposable E-Cigarettes and Associated Health Risks: An Experimental Study. Lin, HC., Buu, A., Su, WC.[2023]

A study using both 2D and 3D in vitro models found that aerosolized flavoured e-liquids from Vuse ePod do not increase toxicity compared to traditional cigarette smoke, suggesting a reduced health risk for users.

The research demonstrated that the cellular toxicity of flavoured e-cigarette products is over 95% lower than that of cigarette smoke, indicating that these products could be beneficial in tobacco harm reduction strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro. Bishop, E., East, N., Miazzi, F., et al.[2023]

The study systematically assessed how different factors, such as e-cig brand, flavor, type, puffing patterns, and voltage, affect the emissions from electronic cigarettes, revealing a complex interaction that influences the health risks associated with their use.

High concentrations of particles (up to 10 million particles/cm3) and harmful substances, including organic compounds and combustion byproducts like benzene and toluene, were detected in e-cig emissions, highlighting potential health risks for users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing electronic cigarette emissions: linking physico-chemical properties to product brand, e-liquid flavoring additives, operational voltage and user puffing patterns. Zhao, J., Nelson, J., Dada, O., et al.[2023]

A study involving 30 college-aged JUUL users found that preferred flavours significantly enhanced user satisfaction, enjoyment, and motivation to use the product compared to a classic tobacco flavour.

Despite both flavour conditions leading to increased nicotine levels, the preferred flavour resulted in a much higher likelihood of continued use, suggesting that restricting flavours could help reduce ENDS appeal among young users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of flavour manipulation on ENDS (JUUL) users' experiences, puffing behaviour and nicotine exposure among US college students. Vargas-Rivera, M., Ebrahimi Kalan, M., Ward-Peterson, M., et al.[2023]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Transitions in device and liquid characteristic groupings among US adults frequently using electronic nicotine delivery systems (ENDS) over three timepoints, 2020-2021. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Combinations of electronic nicotine delivery system device and liquid characteristics among U.S. adults. [2022]

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

Clearing the Haze: What Do We Still Need to Learn about Electronic Nicotine Delivery Systems? [2023]

4. England pubmed.ncbi.nlm.nih.gov

Device and liquid characteristics used with sweet, menthol/mint, and tobacco ENDS liquid flavors: The population-based VAPER study. [2023]

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

Electronic nicotine delivery systems: a policy statement from the American Association for Cancer Research and the American Society of Clinical Oncology. [2022]

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

Electronic nicotine delivery system (ENDS) liquid nicotine exposure in young children presenting to US emergency departments, 2018. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Disposable E-Cigarettes and Associated Health Risks: An Experimental Study. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Assessing electronic cigarette emissions: linking physico-chemical properties to product brand, e-liquid flavoring additives, operational voltage and user puffing patterns. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Effect of flavour manipulation on ENDS (JUUL) users' experiences, puffing behaviour and nicotine exposure among US college students. [2023]