Nicotine Pouches + Lozenges for Smoking Cessation

Overseen By Megan Piper, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Wisconsin, Madison

Must not be taking: Bupropion

Disqualifiers: Psychosis, Bipolar, Pregnant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are using nicotine replacement, varenicline, or bupropion (only for smoking cessation), you will need to stop taking them to participate in the trial. If you are taking bupropion for other reasons, like depression, you cannot join the trial.

What data supports the effectiveness of the treatment Nicotine Pouches + Lozenges for Smoking Cessation?

Research indicates that medicinal nicotine products, like lozenges, have been used successfully to help people quit smoking. Nicotine pouches, such as Zyn, are considered a low-risk alternative to cigarettes and may serve as a novel approach to nicotine replacement therapy. ^{1 2 3 4 5}

Is the combination of nicotine pouches and lozenges safe for human use?

Research suggests that nicotine pouches, like ZYN, may be a lower-risk alternative to traditional tobacco products, but specific safety data for the combination of nicotine pouches and lozenges is not available. Nicotine lozenges have been used as a smoking cessation aid, and while they may have a low risk of abuse, especially among younger individuals, their safety profile is generally considered acceptable for smoking cessation. ^{1 4 6 7 8}

How is the treatment with nicotine pouches and lozenges different from other smoking cessation options?

This treatment is unique because it uses tobacco-free nicotine pouches, which are placed between the lip and gum, offering a low-risk alternative to traditional tobacco products. Unlike other nicotine replacement therapies, these pouches come in various flavors and are marketed as a novel, discreet way to deliver nicotine without tobacco. ^{1 9 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to investigate how well nicotine pouches and nicotine mini lozenges serve as substitutes for cigarettes when people try to switch from smoking to using these alternate nicotine products. Participants will: * Use nicotine pouches, nicotine mini lozenges, or no study product for a week and then try not to smoke for 3 weeks. * Have 6 in-person research visits and 1 follow-up call * Complete questionnaires at each study contact and use a smartphone app to record smoking and study product use

Research Team

Megan Piper, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for individuals who are currently smoking and interested in quitting. Participants will try nicotine pouches or mini lozenges as alternatives to cigarettes. They must be willing to attend several research visits, complete questionnaires, and use a smartphone app to track their usage of products.

Inclusion Criteria

I am 21 years old or older.

Exhaled carbon monoxide ≥ 6 ppm

I haven't used nicotine pouches or smokeless tobacco in the last 6 months.

Exclusion Criteria

I am currently taking bupropion for reasons other than to quit smoking.

Currently pregnant or breastfeeding

I am currently being treated for psychosis or bipolar disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Product Use and Switching

Participants use nicotine pouches, mini lozenges, or no product for 1 week, then attempt to abstain from smoking for 3 weeks

4 weeks

6 in-person visits

Follow-up

Participants are monitored for safety and effectiveness after the switching period

1 week

1 follow-up call

Treatment Details

Interventions

• Mini Nicotine lozenges
• Nicotine Pouches

Trial Overview The study is testing the effectiveness of nicotine pouches and mini lozenges in helping smokers quit by substituting these products for cigarettes. Over a four-week period, participants will first use one of the products for a week followed by an attempt to abstain from smoking for three weeks.

Participant Groups

Group I: Nicotine Mini Lozenges Experimental Treatment 1 Intervention

Participants will use mini lozenges with dosing based on time to first cigarette (2mg - 4mg)

Group II: 6mg Nicotine Pouches Experimental Treatment 1 Intervention

Participants will use 6mg nicotine pouches

Group III: 3mg Nicotine Pouches Experimental Treatment 1 Intervention

Participants will use 3mg nicotine pouches

Group IV: No Study Product Active Control 1 Intervention

Participants randomized to this arm will use a mint candy during two different 30-minute laboratory sessions only.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

A study analyzing 653 Reddit posts about oral nicotine pouches revealed that users predominantly shared positive experiences and product information, indicating a favorable public perception of these tobacco-free products.

The discussions also highlighted a significant interest in quitting traditional nicotine products, with 12.7% of posts focused on using oral nicotine pouches as a cessation tool, suggesting potential for these pouches in harm reduction strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study. Shao, Y., Zou, J., Xie, Z., et al.[2022]

Nicotine pouches are gaining popularity in the UK as tobacco-free products that deliver nicotine when placed between the lip and gum.

The article discusses the composition, legality, and usage patterns of nicotine pouches, as well as potential oral and general health effects associated with their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pouches: a review for the dental team. M Jackson, J., Weke, A., Holliday, R.[2023]

Lucy, a company producing flavored nicotine products, may mislead consumers by marketing its gums, lozenges, and pouches in a way that confuses smoking cessation products with those that maintain nicotine dependence, particularly since only the lozenges are FDA approved for cessation.

The attractive packaging and marketing strategies, which emphasize flavors and downplay nicotine warnings, could appeal to youth and non-users, potentially increasing nicotine initiation rather than promoting cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lucy-Novel Flavored Nicotine Gum, Lozenges, and Pouches: Are They Misleading Consumers? Unger, JB., Barker, J., Cruz, TB., et al.[2023]

Nicotine pouch use in Great Britain is currently rare, with a prevalence of only 0.26% among adults, but it has doubled from November 2020 to October 2021, indicating a growing interest in these products.

The use of nicotine pouches is significantly more common among men, current smokers, and users of other nicotine products like e-cigarettes and nicotine replacement therapies, suggesting that these pouches may appeal more to those already familiar with nicotine consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobacco-free Nicotine Pouch Use in Great Britain: A Representative Population Survey 2020-2021. Tattan-Birch, H., Jackson, SE., Dockrell, M., et al.[2022]

References

1. Switzerland 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). [2023]

2. England pubmed.ncbi.nlm.nih.gov

Randomized crossover trial of the acceptability of snus, nicotine gum, and Zonnic therapy for smoking reduction in heavy smokers. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Nicotine pouch marketing strategies in the USA: an analysis of Zyn, On! and Velo. [2022]

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

Nicotine delivery systems. [2015]

5. Canada pubmed.ncbi.nlm.nih.gov

Tobacco-Derived Nicotine Pouch Brands and Marketing Messages on Internet and Traditional Media: Content Analysis. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Subjective effects of the nicotine lozenge: assessment of abuse liability. [2018]

7. England 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. [2021]

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

Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum. [2023]

9. Canada pubmed.ncbi.nlm.nih.gov

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Nicotine pouches: a review for the dental team. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Lucy-Novel Flavored Nicotine Gum, Lozenges, and Pouches: Are They Misleading Consumers? [2023]

12. England pubmed.ncbi.nlm.nih.gov

Tobacco-free Nicotine Pouch Use in Great Britain: A Representative Population Survey 2020-2021. [2022]