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

Trial Summary

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 6-methyl nicotine e-cigarette safe for humans?

The safety of 6-methyl nicotine e-cigarettes is not well-documented, but studies on e-cigarettes in general show that impurities and potentially harmful chemicals in aerosols are below occupational exposure limits. However, nicotine and its analogs, like 6-methyl nicotine, are associated with health risks, and more research is needed to fully understand their safety. ^{1 2 3 4 5}

How is the 6-methyl-nicotine e-cigarette treatment different from other smoking treatments?

The 6-methyl-nicotine e-cigarette is unique because it uses a synthetic nicotine analog called Metatine, which may bypass certain regulatory requirements that apply to traditional nicotine products. This could potentially offer a different regulatory pathway and market presence compared to conventional nicotine-based e-cigarettes. ^{1 2 6 7 8}

What is the purpose of this trial?

This clinical trial studies the effects, appeal, and abuse liability of 6-methyl nicotine (metatine) electronic cigarettes among young adults.

Research Team

Alayna P Tackett, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols. [2017]

2. United States 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". [2023]

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

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

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

Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine. [2023]

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

Effect of Third Party Components on Emissions from a Pod Style Electronic Cigarette. [2023]

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

Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults. [2023]

7. Italy 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. [2023]

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

A randomised controlled single-centre open-label pharmacokinetic study to examine various approaches of nicotine delivery using electronic cigarettes. [2023]