E-Cigarettes for Smoking

Overseen By Janet Audrain-McGovern, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Smoking cessation medication

Disqualifiers: Substance abuse, Pregnancy, Serious disease, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

210 Participants Needed

Trial Summary

What is the purpose of this trial?

This between-subjects study aims to evaluate the effect of flavor on initial and sustained switching from combustible cigarettes to e-cigarettes among 210 cigarette smokers. After measuring baseline cigarette smoking rate, participants will be randomized to a six-week regimen of fruit-flavored, tobacco-flavored, or menthol-flavored e-cigarettes and be instructed to switch (versus smoking cigarettes) over a 6-week period. Flavor-associated subjective reward and the reinforcing value of flavored e-cigarettes relative to combustible cigarettes will be assessed as mechanisms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using smoking cessation medication. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment E-cigarettes, Electronic Cigarettes, Vaporizers, E-cigs, Vapes for smoking cessation?

Research shows that e-cigarettes can help reduce cigarette consumption and support smoking cessation. In a study, 40% of participants either reduced their cigarette use by more than half or quit smoking entirely after 24 months of using e-cigarettes. ^{1 2 3 4 5}

Is there safety data available for e-cigarettes?

The provided research articles do not contain specific safety data for e-cigarettes or related products like vaporizers or vapes. ^{6 7 8 9 10}

How do e-cigarettes differ from other treatments for smoking cessation?

E-cigarettes are unique because they deliver nicotine without combustion, using a battery-powered device to heat a liquid that produces vapor, mimicking the act of smoking. Unlike traditional nicotine replacement therapies, e-cigarettes offer a variety of flavors and are not yet fully regulated by the FDA, which raises concerns about their long-term health effects. ^{2 11 12 13 14}

Research Team

Janet Audrain-McGovern, Ph.D.

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for smokers over 21 who've smoked at least 5 cigarettes daily for the past year, have tried to quit at least 5 times with medication once, and can give consent. They must live locally for the study duration, not use other nicotine forms regularly, and have a CO level over 10 ppm.

Inclusion Criteria

Able to communicate fluently in English (i.e. speaking, writing, and reading)

Not using any forms of nicotine regularly other than cigarettes

Be willing to switch to e-cigarettes for 6 weeks and use the assigned flavors

Exclusion Criteria

Allergies to either propylene glycol or flavor additives

I am currently using medication to help me stop smoking.

History of substance abuse (other than nicotine dependence) in the past 12 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Baseline smoking rate is established during days 1-5

1 week

2 visits (in-person)

Treatment

Participants are randomized to a six-week regimen of fruit-flavored, tobacco-flavored, or menthol-flavored e-cigarettes and instructed to switch from smoking cigarettes

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for cigarette smoking behavior at the 6-month follow-up

19 weeks

1 visit (in-person)

Treatment Details

Interventions

• E-cigarettes

Trial Overview The study tests if flavors (fruit, tobacco, menthol) in e-cigarettes influence smokers to switch from regular cigarettes. Participants will be randomly assigned one of these flavored e-cigarettes to use for six weeks while their smoking rates and preferences are monitored.

Participant Groups

Group I: Fruit-flavored E-cigarettes Experimental Treatment 1 Intervention

Participants randomized to fruit-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and fruit-flavored nicotine pods. Participants will be able to choose between blueberry or watermelon-flavored pods. They will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior.

Group II: Tobacco-flavored E-cigarettes Active Control 1 Intervention

Participants randomized to tobacco-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and tobacco nicotine pods. Participants will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior.

Group III: Menthol-flavored E-cigarettes Active Control 1 Intervention

Participants randomized to menthol-flavored e-cigarettes will be provided with an e-cigarette device and be instructed to switch from smoking combustible cigarettes to using only the study provided e-cigarette device and menthol nicotine pods. Participants will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior.

E-cigarettes is already approved in European Union, United States, Canada, Japan, United Kingdom for the following indications:

Approved in European Union as E-cigarettes for:

• Smoking cessation aid

Approved in United States as E-cigarettes for:

• No therapeutic indications approved; regulated as tobacco products

Approved in Canada as E-cigarettes for:

• Smoking cessation aid under prescription

Approved in Japan as E-cigarettes for:

• Prescription-only for smoking cessation

Approved in United Kingdom as E-cigarettes for:

• Smoking cessation aid under prescription

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

E-cigarettes have been shown to significantly reduce the desire to smoke and the number of cigarettes smoked per day in small clinical studies, suggesting they may help modify smoking habits.

While e-cigarettes may have fewer adverse effects compared to nicotine patches and can aid in short-term smoking reduction, there is limited evidence for their long-term effectiveness in achieving sustained smoking cessation beyond 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of electronic cigarettes for smoking cessation. Orr, KK., Asal, NJ.[2018]

Smokers are increasingly using e-cigarettes or electronic nicotine delivery systems (ENDS) as alternatives to traditional combustible tobacco products like cigarettes and cigars.

E-cigarettes are often seen as a tool for smoking cessation, providing a different method for nicotine delivery compared to conventional smoking methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of E-Cigarettes and Vaping. [2020]

A survey of 128 North Carolina physicians revealed that 67% believe e-cigarettes can help with smoking cessation, and 35% have recommended them to patients.

Physicians are more likely to recommend e-cigarettes if patients inquire about them or if they perceive e-cigarettes as safer than traditional cigarettes, highlighting the need for FDA regulation to provide clearer guidance on their safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physicians' attitudes and use of e-cigarettes as cessation devices, North Carolina, 2013. Kandra, KL., Ranney, LM., Lee, JG., et al.[2022]

In a study of 40 smokers not intending to quit, long-term use of e-Cigarettes led to a significant reduction in cigarette consumption, with 27.5% of participants achieving over a 50% reduction in daily cigarette use after 24 months.

The e-Cigarette was well tolerated, with only mild side effects reported, and 12.5% of participants achieved complete smoking abstinence, indicating that e-Cigarettes can be an effective tool for reducing smoking in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of electronic cigarette in real-life: a 24-month prospective observational study. Polosa, R., Morjaria, JB., Caponnetto, P., et al.[2022]

The E3 trial is a comprehensive study involving 376 participants over 12 weeks, aimed at evaluating the effectiveness of nicotine e-cigarettes compared to non-nicotine e-cigarettes and no e-cigarettes for smoking cessation, with follow-ups extending to 52 weeks.

This trial will provide crucial data on the efficacy and safety of e-cigarettes as a smoking cessation tool, helping inform healthcare professionals and regulators about their potential role in helping smokers quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Controlled Trial Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation in the General Population: E3 Trial Design. Hébert-Losier, A., Filion, KB., Windle, SB., et al.[2022]

A new standardized strategy for reporting adverse events (AEs) and serious adverse events (SAEs) in substance use disorder (SUD) clinical trials was developed, which aims to reduce the reporting burden while maintaining safety monitoring.

In a review of 17 SUD trials involving 6737 participants, the new strategy showed a significant reduction in irrelevant safety event reporting, leading to a more consistent safety assessment system tailored to the risks associated with specific trial interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for safety reporting in substance abuse trials. Lindblad, R., Campanella, M., Styers, D., et al.[2013]

The study analyzed 16 FDA Drug Safety Communications from 2010 to 2015 and found that 4 of these advisories led to a significant increase in the reporting of specific adverse effects, with reporting odds ratios ranging from 3.9 to 40.6.

However, there was no consistent pattern in reporting changes across all advisories, indicating that the impact of safety warnings on adverse event reporting can vary widely and should be assessed individually.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Safety Advisories and Reporting to the Adverse Event Reporting System (FAERS). Moore, TJ., Morrow, RL., Dormuth, CR., et al.[2021]

The Vaccine Adverse Event Reporting System (VAERS) is a reliable database for assessing vaccine safety, with a good positive predictive value confirmed by multiple studies.

VAERS will play a crucial role in monitoring the safety of new or significantly modified vaccines that are expected to be introduced soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the Vaccine Adverse Event Reporting System database. Geier, DA., Geier, MR.[2019]

The study found a high overlap of safety signals (SDRs) among the EudraVigilance Data Analysis System (EVDAS), FAERS, and VigiBase® databases, with median overlaps of 85% at the Preferred Term level and up to 97.7% when combining High Level Terms with Standardized MedDRA® Queries.

Despite the high overlap, the recall of signals in EVDAS was only about 59.4% to 87.9% of all signals generated across the databases, indicating that while the databases share many similar safety profiles, there are still differences in reporting that can affect signal detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase®. Vogel, U., van Stekelenborg, J., Dreyfus, B., et al.[2021]

In a pooled analysis of 21 clinical trials involving 1468 patients with EGFR mutation-positive non-small cell lung cancer, afatinib was found to cause significantly more severe adverse events, such as rash and diarrhea, compared to erlotinib and gefitinib.

Gefitinib was associated with a higher frequency of severe hepatotoxicity compared to the other two drugs, while the overall rates of severe interstitial lung disease were low and similar across all three EGFR-TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Takeda, M., Okamoto, I., Nakagawa, K.[2022]

E-cigarette use among older adults at risk for or with COPD increased from 2010 to 2016, but current use remained stable at around 5%, indicating a growing interest but limited ongoing use.

The study found that e-cigarette users had worse respiratory health and were less likely to quit conventional cigarettes, suggesting that e-cigarettes do not effectively aid in smoking cessation and may be linked to poorer lung function outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. Bowler, RP., Hansel, NN., Jacobson, S., et al.[2019]

E-cigarettes expose users to harmful chemicals and particulates that can negatively impact cardiovascular and lung health, similar to conventional cigarettes, highlighting the need for caution among users.

Most adults who use e-cigarettes also continue to smoke traditional cigarettes, which complicates efforts to reduce exposure to toxic substances, emphasizing the importance of total abstinence from combustible tobacco for better health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-cigarettes and Atherosclerotic Cardiovascular Disease: What Clinicians and Researchers Need to Know. Darville, A., Hahn, EJ.[2020]

About 26.1% of high school students who have ever used e-cigarettes reported using them for dripping, which involves directly applying e-liquids to heated atomizers to create vapor.

The main reasons for dripping included producing thicker vapor clouds (63.5%) and enhancing flavor (38.7%), with male students and those with more frequent e-cigarette use being more likely to engage in this behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-Cigarettes and "Dripping" Among High-School Youth. Krishnan-Sarin, S., Morean, M., Kong, G., et al.[2022]

E-cigarettes and vaporizers deliver nicotine without combustion, using a liquid that is heated to produce vapor, which mimics the experience of traditional smoking while avoiding some harmful effects of burning tobacco.

Despite being marketed as a safer alternative to smoking, e-cigarettes are not regulated by the FDA, raising concerns about their long-term health effects and safety due to their rapid rise in popularity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-cigarettes in Delaware: An Overview of Concerns of Potential Health Risks & Related Factors. Tullier, S.[2021]

References

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

Efficacy of electronic cigarettes for smoking cessation. [2018]

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

Use of E-Cigarettes and Vaping. [2020]

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

Physicians' attitudes and use of e-cigarettes as cessation devices, North Carolina, 2013. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of electronic cigarette in real-life: a 24-month prospective observational study. [2022]

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

A Randomized Controlled Trial Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation in the General Population: E3 Trial Design. [2022]

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

Strategies for safety reporting in substance abuse trials. [2013]

7. New Zealand pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Safety Advisories and Reporting to the Adverse Event Reporting System (FAERS). [2021]

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

A review of the Vaccine Adverse Event Reporting System database. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase®. [2021]

10. Ireland pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. [2022]

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

Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. [2019]

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

E-cigarettes and Atherosclerotic Cardiovascular Disease: What Clinicians and Researchers Need to Know. [2020]

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

E-Cigarettes and "Dripping" Among High-School Youth. [2022]

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

E-cigarettes in Delaware: An Overview of Concerns of Potential Health Risks & Related Factors. [2021]