E-cigarettes and Nicotine Pouches for Cigarette Smokers

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, Excessive alcohol, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether e-cigarettes or nicotine pouches better assist smokers in reducing cigarette use. Researchers aim to determine which option facilitates the transition from traditional cigarettes by examining changes in health markers. It suits individuals who smoke at least five cigarettes daily, have attempted to quit multiple times, and are open to trying e-cigarettes or nicotine pouches for six weeks. Participants will use either e-cigarettes or nicotine pouches, selecting from various flavors, throughout the study. As an unphased trial, this study provides a unique opportunity to contribute to research that could inform new smoking cessation strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using smoking cessation medication, you will need to stop that to participate.

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

Research has shown that both oral nicotine pouches and e-cigarettes present safety concerns. The FDA has approved some oral nicotine pouches, suggesting they might help adults who smoke regular cigarettes. However, no tobacco product is completely safe. Nicotine pouches can harm young people and pregnant women and pose a choking hazard if swallowed.

E-cigarettes release harmful chemicals like formaldehyde, which can cause lung disease. Studies have found that using only e-cigarettes increases the risk of lung diseases like COPD and high blood pressure. While they might be less harmful than regular cigarettes, e-cigarettes still carry risks.

In summary, although these alternatives might be less harmful than smoking regular cigarettes, they still pose potential health risks. Participants should consider these risks when thinking about switching from regular cigarettes to these alternatives. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using alternative nicotine delivery systems like e-cigarettes and nicotine pouches for cigarette smokers because these methods offer a smoke-free way to satisfy nicotine cravings. Unlike traditional smoking cessation therapies such as nicotine replacement patches or gums, these treatments mimic the hand-to-mouth action and the sensory experience of smoking, which could help ease the transition for smokers. E-cigarettes and nicotine pouches also come in a variety of flavors, providing personalized options that might make quitting more appealing and enjoyable. Moreover, they eliminate the harmful tar and many of the toxic chemicals found in combustible cigarettes, potentially reducing the health risks associated with smoking.

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

This trial will compare the effectiveness of oral nicotine pouches (ONPS) and e-cigarettes (ECIGS) for cigarette smokers. Studies have shown that oral nicotine pouches can help people smoke fewer cigarettes. One study found that using these pouches resulted in lower levels of harmful chemicals, like NNAL, compared to no treatment. However, some evidence suggests they might not be as effective as e-cigarettes for quitting smoking completely.

Research has also indicated that e-cigarettes can help people stop smoking. In real-life situations, e-cigarettes have been linked to a significant drop in cigarette use. One study showed that using e-cigarettes along with regular counseling helped more people quit smoking. Most people who tried e-cigarettes reported smoking fewer regular cigarettes. Participants in this trial will be randomized to receive either oral nicotine pouches or e-cigarettes to assess their effectiveness in reducing cigarette use. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for persistent cigarette smokers over 21 years old who smoke at least 5 cigarettes daily for the past 6 months, have tried to quit smoking at least five times, and are not using other nicotine forms. Participants must have a breath carbon monoxide level above 10 ppm, plan to stay in the area for six weeks, and be able to give informed consent.

Inclusion Criteria

I can fluently speak, write, and read in English.

I am over 21 and have smoked 5 or more cigarettes daily for the last 6 months.

I only use cigarettes, no other nicotine products.

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, followed by laboratory visits to assess ECIG and ONP-associated subjective reward and reinforcing value

1 week

2 visits (in-person)

Treatment

Participants switch from cigarette smoking to ECIGS or ONPS for a six-week period

6 weeks

Weekly supply visits

Follow-up

Participants are monitored for cigarette consumption and biomarkers of exposure at a 6-month follow-up

19 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Alternative Nicotine Delivery Systems

Trial Overview The study compares e-cigarettes (ECIGS) with oral nicotine pouches (ONPS) as alternatives to regular cigarettes among 200 smokers. It's designed to see which substitute reduces harmful biomarkers more effectively over a six-week period while also assessing their satisfaction and preference compared to traditional cigarettes.

How Is the Trial Designed?

Group I: ONPS Experimental Treatment 1 Intervention

Participants randomized to ONPS will be provided with oral nicotine pouches and be instructed to switch from smoking combustible cigarettes to using only the study-provided nicotine pouches. Participants will be able to choose between Original, Mint, Berry, and Citrus flavored nicotine pouches. They will receive their supply of nicotine pouches in 7-day increments, based on baseline smoking behavior.

Group II: ECIGS Experimental Treatment 1 Intervention

Participants randomized to ECIGS 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. Participants will be able to choose between Tobacco, Menthol, Watermelon, and Blueberry flavored nicotine pods. They will receive their supply of nicotine pods in 7-day increments, based on baseline smoking behavior.

Alternative Nicotine Delivery Systems is already approved in United States, European Union for the following indications:

Approved in United States as E-cigarettes for:

• Harm reduction for persistent cigarette smokers

Approved in United States as Oral Nicotine Pouches for:

• Harm reduction for persistent cigarette smokers

Approved in European Union as E-cigarettes for:

• Harm reduction for persistent cigarette smokers

Approved in European Union as Oral Nicotine Pouches for:

• Harm reduction for persistent cigarette smokers

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Oral Nicotine Pouches (ONPs) are gaining popularity, especially among adolescents and young adults, with over 50% of users preferring flavored options like menthol, fruity, and dessert flavors, which may encourage smokers to switch from cigarettes.

The study identified 152 natural and 228 synthetic ONP products, revealing that while tobacco and menthol flavors dominate natural ONPs, fruity and menthol flavors are most common in synthetic ONPs, raising concerns about potential health risks due to their chemical composition and effects on cellular signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification, Perception, and Toxicity of Emerging Flavored Oral Nicotine Pouches. Shaikh, SB., Newton, C., Tung, WC., et al.[2023]

In a study involving adult smokers, nicotine pouches (NPs) showed lower peak nicotine levels (Cmax) and longer time to peak (tmax) compared to traditional cigarettes, indicating a slower nicotine delivery.

Participants reported lower cravings for cigarettes when using NPs, suggesting that these products may have a lower abuse potential and could serve as a safer alternative for smokers looking to switch from cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes. Rensch, J., Liu, J., Wang, J., et al.[2021]

Introducing the nicotine pouch ZYN in the US in 2000 could potentially lead to 249 fewer deaths among a simulated cohort of 100,000 smokers by 2050, translating to approximately 700,000 fewer deaths nationwide.

The model suggests that even with conservative estimates of ZYN's reduced risk compared to smoking, switching to ZYN could significantly lower product-related mortality, highlighting its potential as a safer alternative for smokers not intending to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimating the public health impact had tobacco-free nicotine pouches been introduced into the US in 2000. Lee, PN., Fry, JS., Ljung, T.[2022]

Nicotine pouches, a new product category, are being marketed with minimal research and regulatory oversight, highlighting significant gaps in understanding their potential harms and benefits.

The commentary suggests a comprehensive assessment approach to inform regulatory policies, aiming to enhance public health outcomes while reducing unintended negative effects associated with nicotine pouch use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? Patwardhan, S., Fagerström, K.[2023]

Vaporised nicotine products (VNPs) can effectively help individuals in alcohol and other drug treatment manage nicotine cravings and mimic the hand-to-mouth action of smoking, making them a promising smoking cessation aid.

However, participants faced challenges such as device maintenance, regulatory limitations, and the difficulty of quitting tobacco while also trying to reduce cannabis use, which could hinder the effectiveness of VNPs in smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barriers and facilitators to using vaporised nicotine products as smoking cessation aids among people receiving treatment for substance use disorder. Lum, A., Skelton, E., Robinson, M., et al.[2021]

In a study involving 40 adult smokers, the JUUL2 prototype with 18 mg/mL nicotine delivered more nicotine than the JUUL 59 mg/mL, suggesting it could be more effective in helping smokers switch from combustible cigarettes.

The JUUL2 prototype 40 mg/mL was found to be more aversive than other products, indicating it may need adjustments to be appealing for adult smokers, while the JUUL products generally provided greater satisfaction and craving reduction compared to the IQOS heated tobacco product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and subjective assessment of prototype JUUL2 electronic nicotine delivery system in two nicotine concentrations, JUUL system, IQOS, and combustible cigarette. Goldenson, NI., Augustson, EM., Chen, J., et al.[2022]

ZYN nicotine pouches contain no nitrosamines or polycyclic aromatic hydrocarbons (PAHs), indicating a potentially lower risk profile compared to traditional tobacco products, which often contain harmful constituents.

The levels of harmful and potentially harmful constituents (HPHCs) in ZYN were found to be similar to those in nicotine replacement therapy (NRT) products, suggesting that ZYN may be a safer alternative for nicotine delivery compared to moist snuff, which had significantly higher levels of harmful compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs). Back, S., Masser, AE., Rutqvist, LE., et al.[2023]

A study analyzing nicotine pouch advertising from January 2019 to September 2021 found that Zyn and Velo dominated the market, accounting for 44.4% and 52.8% of 286 unique ads, respectively, with a total expenditure of nearly $24.8 million, primarily on radio and television.

The advertising themes heavily emphasized 'freedom' and 'flavour', with Zyn focusing on brand identity and Velo on innovation, highlighting the need for regulatory oversight to understand the impact of these marketing strategies on consumers, especially young people.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pouch marketing strategies in the USA: an analysis of Zyn, On! and Velo. Duan, Z., Henriksen, L., Vallone, D., et al.[2022]

In a study involving 63 smokers, both snus and Zonnic were preferred over nicotine gum, showing greater effectiveness in reducing smoking urges and causing fewer side effects.

Participants experienced significant reductions in smoking (33% for gum, 37% for snus, and 42% for Zonnic), indicating that snus and Zonnic could be promising alternatives for nicotine replacement therapy, warranting further research on their long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover trial of the acceptability of snus, nicotine gum, and Zonnic therapy for smoking reduction in heavy smokers. Caldwell, B., Burgess, C., Crane, J.[2022]

Medicinal nicotine has significantly improved smoking cessation rates over the past 20 years, with various products like patches, gum, and inhalers available to help smokers quit.

Innovative nicotine delivery methods, such as high-dose patches and new forms like drinks and lollipops, are being developed to enhance cessation success and manage withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine delivery systems. Shiffman, S., Fant, RV., Buchhalter, AR., et al.[2015]

The novel tobacco-free nicotine pouch, ZYN, delivers nicotine effectively, with the 6 mg and 8 mg doses providing similar or faster nicotine absorption compared to traditional smokeless products like General snus and Longhorn moist snuff.

ZYN products showed a higher extraction fraction of nicotine (50-59%) compared to General snus (32%) and Longhorn moist snuff (19%), indicating a more efficient delivery of nicotine without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff. Lunell, E., Fagerström, K., Hughes, J., et al.[2021]

The study found that Zyn Chill, marketed as 'Flavour-Ban Approved', activates the TRPM8 receptor, providing a cooling sensation, despite being advertised as unflavoured, indicating misleading marketing practices.

Chemical analysis revealed that Zyn Chill contains WS-3, a synthetic cooling agent, while mint-flavoured ONPs contain both WS-3 and mint flavourants, suggesting that these products still have flavoring agents that could appeal to consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic cooling agent in oral nicotine pouch products marketed as 'Flavour-Ban Approved'. Jabba, SV., Erythropel, HC., Woodrow, JG., et al.[2023]

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