Nicotine Levels in E-Cigarettes for Tobacco-Related Cancer Prevention

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: CYP2A6 inducers

Disqualifiers: Pregnancy, Lung disease, Cardiovascular, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

350 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications that affect the CYP2A6 enzyme, like rifampicin or dexamethasone.

What data supports the effectiveness of the treatment 'Manipulating E-Cigarette Nicotine, Electronic Nicotine Delivery Systems (ENDS), Vaping Products, E-Cigarettes' for tobacco-related cancer prevention?

Research suggests that e-cigarettes, as a form of electronic nicotine delivery systems (ENDS), may help people reduce or quit smoking by delivering nicotine without the harmful combustion products found in traditional cigarettes. Studies indicate that smokers using ENDS tend to reduce their cigarette consumption, which could potentially lower their risk of tobacco-related cancers. ^{1 2 3 4 5}

Are e-cigarettes safe for humans?

E-cigarettes, also known as electronic nicotine delivery systems (ENDS), are considered less harmful than traditional cigarettes because they don't burn tobacco, but they still deliver nicotine and other chemicals that may affect heart and lung health. The long-term safety of e-cigarettes is not yet fully understood, and there are concerns about their use, especially among young people. ^{1 5 6 7 8}

How does the treatment using nicotine levels in e-cigarettes differ from other treatments for tobacco-related cancer prevention?

This treatment is unique because it uses electronic nicotine delivery systems (ENDS) like e-cigarettes to deliver nicotine without burning tobacco, potentially reducing exposure to harmful chemicals found in traditional cigarettes. Unlike other treatments, it focuses on harm reduction by lowering toxicant levels while still providing nicotine, which may help in smoking cessation efforts. ^{1 6 8 9 10}

What is the purpose of this trial?

This clinical trial explores the manipulation of e-cigarette (EC) nicotine to promote public health. Researchers are trying to understand and gather information about how the strength, form, and structure of nicotine in products play a significant role in their potential for addiction and how they might affect health risks. The information gained from this study may allow researchers to understand how these aspects of nicotine influence the potential for addiction, how people puff on ECs, how the body processes nicotine, and any potential harmful effects it might have on health. Exploring these specific characteristics of nicotine may also determine if an EC product standard could help identify optimal nicotine levels for users.

Research Team

Theodore L. Wagener, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for individuals interested in the effects of e-cigarette nicotine on health. It's not specified who can't join, but typically participants should be healthy adults, possibly smokers or e-cigarette users.

Inclusion Criteria

I can avoid nicotine, tobacco, and marijuana for 12 hours before visits.

I am 21-24, use e-cigarettes only, and have smoked less than 10 cigarettes ever.

I am a smoker aged 25-65 and interested in trying an electronic cigarette.

Exclusion Criteria

I do not use tobacco products daily except for e-cigarettes or cigarettes.

Currently attempting to quit nicotine or tobacco products

I have not been diagnosed with new or worsening heart problems in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 (Study 1)

Participants are randomized to the order of 8 e-liquid combinations varying in nicotine concentration, form, and isomer. They participate in a 10-puff vaping session over 5 minutes followed by a 60-minute washout period and an ad libitum puffing session over 60 minutes at each lab visit.

8 lab visits, up to 4 hours each

8 visits (in-person)

Phase 2 (Study 2)

Participants are randomized to the order of 20 e-liquid combinations varying in concentration, FB fractions, and isomer. They take part in a 2-puff vaping session with each of the 20 study e-liquids with a 10-minute washout period between each session, grouped into two blocks of 10 separated by a 30-minute resting session.

1 lab visit, up to 6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Manipulating E-Cigarette Nicotine

Trial Overview The study investigates how manipulating nicotine levels in e-cigarettes affects addiction potential and health risks. Participants will undergo vaping sessions, provide biospecimens, have their carbon monoxide levels measured, and complete surveys.

Participant Groups

Group I: Phase 2, Arm 9 (High, 45%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group II: Phase 2, Arm 8 (Low, 25%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group III: Phase 2, Arm 7 (Low, 25%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group IV: Phase 2, Arm 6 (High, 25%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group V: Phase 2, Arm 5 (High, 25%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group VI: Phase 2, Arm 4 (Low, 5%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group VII: Phase 2, Arm 3 (Low, 5%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group VIII: Phase 2, Arm 20 (Low, 85%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group IX: Phase 2, Arm 2 (High, 5%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group X: Phase 2, Arm 19 (Low, 85%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XI: Phase 2, Arm 18 (High, 85%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XII: Phase 2, Arm 17 (High, 85%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XIII: Phase 2, Arm 16 (Low, 65%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XIV: Phase 2, Arm 15 (Low, 65%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XV: Phase 2, Arm 14 (High , 65%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XVI: Phase 2, Arm 13 (High , 65%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XVII: Phase 2, Arm 12 (Low, 45%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XVIII: Phase 2, Arm 11 (Low, 45%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XIX: Phase 2, Arm 10 (High, 45%, R/S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XX: Phase 2, Arm 1 (High, 5%, S) Experimental Treatment 4 Interventions

Participants vape 20 different study e-liquids varying in concentration (low \[20 mg/g\] or high \[50 mg/g\]), freebase nicotine percentage (5%, 25%, 45%, 65%, or 85%), and isomer (S-nicotine or R/S nicotine) using the e-cig study device during two visits.

Group XXI: Phase 1, Arm 8 (Low, NicH+, R/S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXII: Phase 1, Arm 7 (Low, NicH+, S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXIII: Phase 1, Arm 6 (High, NicH+, R/S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXIV: Phase 1, Arm 5 (High, NicH+, S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXV: Phase 1, Arm 4 (Low, Nic, R/S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXVI: Phase 1, Arm 3 (Low, Nic, S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXVII: Phase 1, Arm 2 (High, Nic, R/S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Group XXVIII: Phase 1, Arm 1 (High, Nic, S) Experimental Treatment 4 Interventions

Participants are randomized to vape one out of the eight study e-liquids in a 10-puff vaping session over 5 minutes using the e-cig study device and then in an ad libitum puffing session over 60 minutes. The 8 e-liquids vary in nicotine concentration (low \[20 mg/g\] or high \[50 mg/g\]), form (Nic or NicH+), and isomer (S-nicotine or R/S nicotine).

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

Electronic nicotine delivery systems (ENDS), like e-cigarettes, may help smokers quit by providing nicotine without the harmful combustion products found in traditional cigarettes, potentially exposing users to lower levels of toxicants.

However, the long-term safety of ENDS is still unknown, and there are concerns about their use among youth, which could limit their effectiveness as smoking cessation aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame. Benowitz, NL., St Helen, G., Liakoni, E.[2023]

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]

Electronic cigarettes (e.cig.), or electronic nicotine delivery systems (ENDS), may help reduce smoking prevalence due to their ability to deliver nicotine effectively, potentially aiding smokers in quitting.

However, the current lack of regulations and established risk/benefit ratios for ENDS means that their safety and efficacy as smoking cessation aids remain uncertain, highlighting the need for evidence-based knowledge in public health discussions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Electronic cigarettes: A therapeutic tool, a social phenomenon or a business?]. Berlin, I.[2017]

In a randomized trial involving 68 adult smokers, those using electronic nicotine delivery systems (ENDS) showed a significant reduction in cigarette smoking compared to a control group, indicating potential efficacy in smoking cessation.

Participants using the higher nicotine (24 mg) ENDS were more likely to continue using the product and make independent purchases, suggesting that higher nicotine delivery may enhance user engagement and support smoking reduction efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Naturalistic, Randomized Pilot Trial of E-Cigarettes: Uptake, Exposure, and Behavioral Effects. Carpenter, MJ., Heckman, BW., Wahlquist, AE., et al.[2018]

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]

Many electronic nicotine delivery systems (ENDS) contain varying amounts of nicotine that do not match the concentrations labeled on the cartridges, indicating a lack of consistency and reliability in these products.

The presence of chemicals like propylene glycol and glycerol in ENDS raises safety concerns, as limited information is available about the actual contents, which could affect both recreational users and those attempting to quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective. Cheah, NP., Chong, NW., Tan, J., et al.[2022]

Electronic nicotine delivery systems (ENDS), like e-cigarettes, are increasingly popular but their overall health impacts are still unclear, necessitating further research to understand their role in smoking cessation and potential risks, especially for youth.

The American Association for Cancer Research and the American Society of Clinical Oncology recommend strict regulations on ENDS, including ingredient transparency, childproof packaging, and restrictions on marketing to youth, to mitigate potential harms.

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]

E-cigarettes (ENDS) are considered a potential harm reduction tool for smoking cessation, as they do not produce harmful combustion products like traditional cigarettes, but they still deliver various harmful chemicals that raise concerns for cardiovascular and respiratory health.

There is a lack of long-term safety data on ENDS, and while they may help some adults quit smoking, their rising popularity among youth poses a risk of nicotine addiction, highlighting the need for careful regulation and clinician awareness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-Cigarettes Reexamined: Product Toxicity. Pipe, AL., Mir, H.[2022]

In a study of 2475 adult smokers transitioning to electronic nicotine delivery systems (ENDS), those who quit tobacco entirely showed significant reductions in various harmful biomarkers of tobacco exposure, including nicotine metabolites and tobacco-specific nitrosamines (TSNAs).

Smokers who became dual users of cigarettes and ENDS experienced some reductions in certain biomarkers, but these were less pronounced and depended on a significant reduction in cigarette consumption, indicating that complete cessation or exclusive ENDS use is more effective for reducing tobacco exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Biomarkers of Tobacco Exposure among Cigarette Smokers Transitioning to ENDS Use: The Population Assessment of Tobacco and Health Study, 2013-2015. Anic, GM., Rostron, BL., Hammad, HT., et al.[2023]

Between 2012 and 2017, there was a nearly sixfold increase in calls to the British Columbia Poison Centre regarding exposures to electronic nicotine delivery systems (ENDS), primarily due to accidental ingestions in young children, particularly those aged 4 years or less.

Of the 186 unique exposures recorded, 46.8% resulted in reported symptoms, highlighting the need for regulatory measures to reduce children's access to ENDS and improve product safety through better labeling and packaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarette exposures reported to the British Columbia Drug and Poison Information Centre: an observational case series. Choi, A., Le, M., Rahim, T., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame. [2023]

2. 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]

3. France pubmed.ncbi.nlm.nih.gov

[Electronic cigarettes: A therapeutic tool, a social phenomenon or a business?]. [2017]

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

A Naturalistic, Randomized Pilot Trial of E-Cigarettes: Uptake, Exposure, and Behavioral Effects. [2018]

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

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

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

Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

E-Cigarettes Reexamined: Product Toxicity. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Changes in Biomarkers of Tobacco Exposure among Cigarette Smokers Transitioning to ENDS Use: The Population Assessment of Tobacco and Health Study, 2013-2015. [2023]

10. Canada pubmed.ncbi.nlm.nih.gov

Electronic cigarette exposures reported to the British Columbia Drug and Poison Information Centre: an observational case series. [2022]