6-Methyl Nicotine E-Cigarettes for Smoking

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Disqualifiers: COVID-19, Psychiatric, Cardiac, Lung, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 sessions

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how 6-methyl nicotine (metatine) e-cigarettes affect young adults who already use nicotine e-cigarettes. Researchers aim to understand the effects, appeal, and potential for addiction. Participants will try either their own e-cigarette, a regular nicotine e-cigarette, or a fruit-flavored metatine e-cigarette. Individuals aged 21-34 who use nicotine e-cigarettes weekly and are willing to follow the trial guidelines may be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on e-cigarette use.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, you must abstain from using any e-cigarette at least 12 hours before the lab sessions.

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

Research has shown that 6-methyl nicotine, the main ingredient in these e-cigarettes, raises safety concerns. Studies have found it causes more cell damage and stress inside cells compared to regular nicotine. These findings come from lab tests with varying amounts of the substance.

Some reports suggest that 6-methyl nicotine might be more harmful than regular nicotine, especially in animals. However, there isn't enough information yet about its safety for humans. Scientists continue to work on understanding its effects better.

Since this trial is labeled "Not Applicable" for its phase, it might lack the safety information found in later-phase trials. This indicates much remains to be learned about how people handle 6-methyl nicotine e-cigarettes. Prospective participants should discuss any concerns with the researchers or a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for smoking cessation rely on traditional nicotine replacement therapies like patches, gums, or e-cigarettes containing standard nicotine. However, the 6-methyl-nicotine (metatine) e-cigarette offers a unique twist. Metatine is a modified form of nicotine that could potentially offer a different experience for smokers, which might help reduce cravings more effectively or offer a more satisfying alternative. Researchers are excited because this could lead to a new way to help people quit smoking by targeting their addiction in a novel manner. If successful, metatine could change the landscape of smoking cessation options.

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

Research has shown that e-cigarettes, including those containing 6-methyl nicotine (metatine), can be as effective as nicotine patches in helping people quit smoking over six months. In this trial, participants will use either their personal nicotine e-cigarette, a 6-methyl nicotine (metatine) e-cigarette, or a standard nicotine e-cigarette. However, success rates for quitting are usually low. Studies have found that while e-cigarettes can reduce exposure to some harmful chemicals found in regular cigarettes, they also pose potential risks, such as DNA damage. Despite these risks, many people believe e-cigarettes are as effective as other nicotine replacement methods for quitting smoking. It's important to consider these factors when deciding to use e-cigarettes to stop smoking. ^{6 7 8 9 10}

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 English-speaking young adults aged 21-34 who use nicotine e-cigarettes at least weekly. Participants must abstain from vaping 12 hours before lab sessions and cannot be pregnant, planning pregnancy, or breastfeeding. Those with bleeding disorders, severe psychiatric conditions, recent heart issues, COVID-19 infection or hospitalization, or serious lung diseases are excluded.

Inclusion Criteria

Willing to provide informed consent and abstain from using any e-cigarette at least 12 hours prior to the three lab sessions

Current nicotine EC user (defined as ≥ weekly use over the past 3 months)

I am between 21 and 34 years old.

Exclusion Criteria

Currently pregnant, planning to become pregnant, or breastfeeding (will be verified with urine pregnancy test)

Have hemophilia or another type of bleeding disorder

Unstable or significant psychiatric conditions (past and stable conditions will be allowed)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants attend 3 sessions where they are randomized to 1 of 3 types of e-cigarette and use the e-cigarette ad-libitum for 30 minutes, with 4 blood draws during the session

3 sessions

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

• 6-methyl-nicotine (metatine) e-cigarette

Trial Overview The study investigates the effects of a new type of e-cigarette containing 6-methyl-nicotine (metatine) on appeal and potential for abuse among users. It involves biospecimen collection, using participants' preferred e-cigarettes as well as metatine ones in lab settings while monitoring their vaping behavior.

How Is the Trial Designed?

Group I: Participant's personal nicotine e-cigarette Active Control 4 Interventions

The study participant's own preferred e-cigarette will be used for this condition.

Group II: 6-methyl nicotine (metatine) e-cigarette Active Control 4 Interventions

A fruit flavored commercially available metatine e-cigarette will be used for this condition.

Group III: Nicotine e-cigarette Active Control 4 Interventions

A fruit flavored commercially available nicotine e-cigarette will be used for this condition.

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

A study involving 2,094 young adults over four years found that those who used e-cigarettes in the past 30 days had significantly higher odds of experiencing respiratory symptoms such as wheeze, bronchitic symptoms, and shortness of breath compared to non-users.

The associations between e-cigarette use and respiratory symptoms remained significant even after accounting for other factors like cigarette and cannabis use, suggesting that e-cigarettes may pose a risk for respiratory health in young adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults. Tackett, AP., Urman, R., Barrington-Trimis, J., et al.[2023]

The study found that the Vype ePen3 e-cigarette, which delivers a greater aerosol mass, provides higher nicotine bioavailability compared to the Vype ePen, suggesting it may be more effective for smokers switching to e-cigarettes.

Protonated nicotine formulations resulted in significantly higher nicotine delivery than unprotonated versions, indicating that optimizing nicotine formulation can enhance user satisfaction and acceptance of e-cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled single-centre open-label pharmacokinetic study to examine various approaches of nicotine delivery using electronic cigarettes. Ebajemito, JK., McEwan, M., Gale, N., et al.[2023]

A new, quick, and reliable method using isotope dilution LC-MS/MS has been developed to measure nicotine and its metabolites (cotinine and 3-OH-cotinine) in just 60 μL of human urine, which can help assess nicotine exposure and related health risks.

The method provides measurable ranges for nicotine (10-2500 ng/mL) and cotinine (20-5000 ng/mL), making it a useful tool for evaluating the impact of nicotine-containing products on health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation of Urine Nicotine, Cotinine, and 3-OH-Cotinine by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Li, W., Zhang, XS., Noguez, J.[2023]

This study analyzed e-liquids and aerosols from MarkTen® e-cigarettes, finding that common impurities and potentially harmful chemicals were present, but at levels below occupational exposure limits, suggesting a lower immediate risk to users.

The research highlighted that while e-cigarettes contain ingredients like propylene glycol and glycerin that can produce harmful compounds when heated, the detected levels of these chemicals in the aerosols were not considered hazardous based on current safety guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols. Flora, JW., Meruva, N., Huang, CB., et al.[2017]

The FDA now regulates all tobacco products containing nicotine, including synthetic forms, requiring manufacturers to submit premarket applications, which is crucial for ensuring product safety and efficacy.

A new e-cigarette product called Spree Bar, marketed as 'PMTA exempt' and containing a synthetic nicotine analog called 6-methyl nicotine, raises concerns about regulatory loopholes that could allow manufacturers to bypass existing tobacco regulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An electronic cigarette pod system delivering 6-methyl nicotine, a synthetic nicotine analog, marketed in the United States as "PMTA exempt". Jordt, SE., Jabba, SV., Silinski, P., et al.[2023]

In a study involving 15 healthy adult smokers, e-cigarettes with nicotine salts provided a rate of nicotine absorption comparable to conventional cigarettes, but did not deliver more nicotine overall.

While the e-cigarettes were well tolerated and reduced the desire to smoke, the subjective satisfaction from using them was lower than that from smoking conventional cigarettes, indicating that they may not fully replace the satisfaction provided by traditional smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic profiles of cigarettes and e-cigarettes with nicotine salt formulations in US adult smokers. O'Connell, G., Pritchard, JD., Prue, C., et al.[2023]

A health risk assessment of nicotine in cigarette smokers revealed significant consumer risk, with margin of exposure (MOE) values indicating potential toxicity similar to other harmful tobacco toxicants like acrolein and formaldehyde.

The study highlighted the urgent need for long-term animal testing on nicotine due to insufficient toxicological data, especially concerning its cancer risk, and emphasized the importance of addressing nicotine risks in electronic cigarettes and smokeless tobacco products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine. Baumung, C., Rehm, J., Franke, H., et al.[2023]

Third-party refillable reservoirs for electronic nicotine delivery systems (ENDS) produce significantly higher total particulate matter (TPM) and nicotine emissions compared to manufacturer-supplied single-use reservoirs, with TPM yield per puff being 5.6 times greater.

The study highlights that using third-party pods may increase toxicant exposure for consumers, suggesting a need for regulatory oversight by the FDA to ensure safety and limit harmful additives in e-liquids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Third Party Components on Emissions from a Pod Style Electronic Cigarette. Hensel, EC., Sarles, SE., Nuss, CJ., et al.[2023]

Citations

1. researchgate.net researchgate.net/publication/391655306_6-methyl_Nicotine_in_Electronic_Cigarettes_Chemical_Analysis_and_Toxicological_Properties

6-methyl Nicotine in Electronic Cigarettes We aimed to describe e-liquid flavors and nicotine concentration use over 6 months in a prospective cohort of smokers willing to quit with ENDS. METHODS We ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5469426/

Electronic Cigarettes. Potential Harms and Benefits - PMC e-Cigarettes with or without nicotine were as effective as nicotine patches in achieving 6-month smoking cessation. Notably, cessation rates were quite low in ...

3. pnas.org pnas.org/doi/10.1073/pnas.1718185115

E-cigarette smoke damages DNA and reduces repair ... In fact, recent studies show that E-cig smokers, similar to individuals on nicotine replacement therapy, have 97% less 4-(methylnitrosamino)-1-(3-pyridyl)-1- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5937152/

Electronic cigarettes: an aid in smoking cessation, or a new ... This analysis presents a brief overview of currently available evidence and gaps in research covering these three factors.

5. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub7/references

Electronic cigarettes for smoking cessation Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach. Addiction: Science & Clinical ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S037842742500013X

Emerging nicotine analog 6-methyl nicotine increases ... 6-MN-contained e-liquids significantly increased cytotoxicity and intracellular ROS induction in a dose-specific manner compared to nicotine.

7. reporter.nih.gov reporter.nih.gov/project-details/11119068

Effects of vaping-induced oxidation on nicotine analogs e ... Research indicates that 6- methyl nicotine has similar physiological effects to nicotine but raises more significant safety concerns, necessitating further ...

8. medicine.yale.edu medicine.yale.edu/news-article/novel-e-cigarette-products-marketed-to-contain-nicotine-analogs-instead-of-nicotine-show-discrepancies-between-label-information-and-contents/

Novel E-Cigarette Products Marketed to Contain Nicotine ... According to the scientists, the inhalation toxicity and addictive properties of these chemicals in humans, like 6-methyl nicotine (6MN) and ...

9. publications.aap.org publications.aap.org/pediatrics/article/156/2/e2024070484/202426/Awareness-and-Use-of-Vaping-Products-With-a

Awareness and Use of Vaping Products With a Nicotine ... In this nonprobability convenience US AYA sample, awareness and ever-use of 6-methyl-nicotine products were appreciable and overrepresented ...

10. scientificamerican.com scientificamerican.com/article/nicotine-analogs-pose-possible-health-risks-yet-evade-regulation/

Vape Additives that Mimic Nicotine Are Potent—and ... But data on their safety in humans are lacking. ... In rodents, the lethal dose for 6-methylnicotine is smaller than for nicotine.