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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether different flavors of e-cigarettes (also known as electronic cigarettes or vapes) can help people switch from regular cigarettes. Participants will try fruit, tobacco, or menthol-flavored e-cigarettes over six weeks to determine which flavor most effectively encourages the switch. The trial seeks individuals who have smoked at least five cigarettes a day for the past year and have unsuccessfully attempted to quit multiple times. As an unphased trial, this study provides a unique opportunity to explore new methods for quitting smoking and identify the most effective flavor.

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.

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

Research shows that e-cigarettes, regardless of flavor, pose certain health risks. Studies on fruit-flavored e-cigarettes suggest users might have a higher chance of experiencing a dry cough at night. Vaping in general links to breathing problems and possible organ damage.

For tobacco-flavored e-cigarettes, evidence indicates that even though they might seem safer than regular cigarettes, they still carry risks like lung damage and addiction. The FDA has approved some tobacco-flavored e-cigarette products after thorough testing, but this doesn't mean they are completely safe.

Regarding menthol-flavored e-cigarettes, data shows that menthol can harm the lungs and affect their function. Although the FDA has also approved some menthol-flavored products, they still have health risks.

In summary, while e-cigarettes might be less harmful than traditional cigarettes, they are not without dangers. Participants should consider these possible side effects when deciding to join a trial involving e-cigarettes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using e-cigarettes as a smoking cessation method because they offer a novel way to potentially reduce harm compared to traditional cigarettes. Unlike conventional nicotine replacement therapies like patches or gums, e-cigarettes mimic the physical and behavioral experience of smoking, which can be appealing to smokers. The trial explores different flavors—fruit, tobacco, and menthol—which could cater to personal preferences, making it easier for individuals to switch from combustible cigarettes. By providing a familiar experience with potentially reduced risks, e-cigarettes might offer a more effective and satisfying alternative for those looking to quit smoking.

What evidence suggests that this trial's e-cigarette treatments could be effective for smoking cessation?

This trial will compare the effectiveness of different flavored e-cigarettes in helping participants quit smoking traditional cigarettes. Research has shown that e-cigarettes, especially those with sweet or fruity flavors, can aid smoking cessation. Participants in this trial will receive either fruit-flavored, tobacco-flavored, or menthol-flavored e-cigarettes through randomization. Studies have found that people using sweet-flavored e-cigarettes were more likely to stop smoking, at least temporarily. Adding tobacco-flavored e-cigarettes to regular quit-smoking programs has led to more successful quitting. Menthol-flavored e-cigarettes also reduce the urge to smoke more effectively than tobacco-flavored ones. Overall, while e-cigarettes appear to be a helpful tool for quitting smoking, the flavor might influence their success. ^{6 7 8 9 10}

Who Is on the Research Team?

Janet Audrain-McGovern, Ph.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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