Nicotine Pouches for Tobacco Addiction

Recruiting at 1 trial location

Overseen By Jonathan Foulds, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Milton S. Hershey Medical Center

Disqualifiers: Pregnancy, Respiratory diseases, Kidney disease, 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: Unknown

Duration: 16 weeks

375 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to understand the health effects of a new oral nicotine pouch, and also to understand if this product can help reduce traditional cigarette smoking. The main aims are: 1. Understand the impact of nicotine pouch use on toxicant exposure biomarkers, and indicators of potential harms to health. 2. Examine the influence of nicotine pouch use on conventional tobacco product use (cigarettes). Participants will be randomized to one of six nicotine pouch groups (3 nicotine strengths, each with 2 potential flavors) to use over 16 weeks and asked to reduce their cigarette smoking over that time by at least 75% by substituting with the use of the nicotine pouches. Researchers will compare the outcomes of the different nicotine pouch strengths and flavors to each other. Participants will be asked to complete study questionnaires and provide urine, exhaled carbon monoxide, and mouth cell samples, and other health measurements.

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, if you have a serious medical condition or are on medications that might affect your safety or the study's results, you may not be eligible to participate.

What data supports the effectiveness of nicotine pouches as a treatment for tobacco addiction?

Research suggests that oral nicotine products, like pouches, can serve as a low-risk alternative to cigarettes and may help people quit smoking by delivering nicotine without the harmful chemicals found in tobacco. These products are gaining popularity and are considered a novel approach to nicotine replacement therapy, which has been shown to increase quit rates among smokers. ^{1 2 3 4 5}

Is there any safety data available for nicotine pouches used in humans?

There is limited safety data on nicotine pouches, but they are considered a low-risk alternative to cigarettes and traditional smokeless tobacco products. However, most people are uncertain about their relative harm compared to cigarettes and e-cigarettes. ^{3 5 6 7 8}

How are nicotine pouches different from other treatments for tobacco addiction?

Nicotine pouches are a novel, tobacco-free option for delivering nicotine orally, offering a potentially lower-risk alternative to cigarettes and traditional smokeless tobacco products like snus. Unlike some nicotine replacement therapies (NRTs), these pouches do not contain tobacco and are marketed as 'tobacco-free', which may appeal to those looking to reduce tobacco use while still managing nicotine cravings. ^{1 3 5 6 8}

Research Team

Jonathan Foulds, PhD

Principal Investigator

Penn State College of Medicine

Eligibility Criteria

This trial is for daily smokers with a baseline exhaled CO of ≥6 ppm, who read and write English, have internet access, and want to cut down smoking by at least 50% using nicotine pouches. Not for pregnant women, those planning pregnancy soon, people with recent severe illnesses or hospitalizations, serious respiratory diseases, kidney/liver disease or heavy illegal drug use.

Inclusion Criteria

Exhaled CO measurement of ≥ 6 parts per million at baseline

Access to e-mail and a smartphone/computer that has reliable internet connection

I understand the study and agree to participate.

Exclusion Criteria

You have been using illegal drugs regularly (every day or every week) in the past 3 months.

Recent unstable illness that may increase risks of participation or ability to participate fully (e.g. hospitalization for a mental health condition or substance use disorder in prior 6 months, stroke or myocardial infarction in the past year)

You intend to stop smoking within the next month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of six nicotine pouch groups to use over 16 weeks and asked to reduce cigarette smoking by at least 75% by substituting with nicotine pouches.

16 weeks

Multiple visits for sample collection and questionnaires

Follow-up

Participants are encouraged to quit smoking and connected to cessation services, followed-up 4 weeks later to assess the influence of nicotine content on quitting.

4 weeks

Treatment Details

Interventions

• Nicotine Pouches

Trial Overview The study tests new oral nicotine pouches in different strengths (0 mg, 3 mg, 6 mg) and flavors (Smooth and Wintergreen), aiming to reduce cigarette use by substituting these pouches over 16 weeks. Participants will be randomly assigned a product variant to see how it affects health indicators and smoking habits.

Participant Groups

Group I: 6 mg + Wintergreen flavor Experimental Treatment 2 Interventions

Participants are provided with high strength (6 mg) nicotine pouches with wintergreen flavor.

Group II: 6 mg + Smooth flavor Experimental Treatment 2 Interventions

Participants are provided with high strength (6 mg) nicotine pouches with smooth flavor.

Group III: 3 mg + Wintergreen flavor Experimental Treatment 2 Interventions

Participants are provided with medium strength (3 mg) nicotine pouches with wintergreen flavor.

Group IV: 3 mg + Smooth flavor Experimental Treatment 2 Interventions

Participants are provided with medium strength (3 mg) nicotine pouches with smooth flavor.

Group V: 0 mg + Wintergreen flavor Experimental Treatment 2 Interventions

Participants are provided with zero strength (0 mg) nicotine pouches with wintergreen flavor.

Group VI: 0 mg + Smooth flavor Experimental Treatment 2 Interventions

Participants are provided with zero strength (0 mg) nicotine pouches with smooth flavor.

Nicotine Pouches is already approved in United States, European Union for the following indications:

Approved in United States as Nicotine Pouches for:

• Smoking cessation aid
• Nicotine replacement therapy

Approved in European Union as Nicotine Pouches for:

• Smoking cessation aid
• Nicotine replacement therapy

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

A survey of 6,131 U.S. participants aged 13-40 revealed that 33% had ever used oral nicotine products, with higher usage rates among those aged 21-40 compared to those under 21.

Marketing significantly influences the likelihood of purchasing oral nicotine products, especially among younger users, who are more likely to buy products like Zyn pouches when they perceive marketing messages about appealing flavors and social comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use, marketing, and appeal of oral nicotine products among adolescents, young adults, and adults. Gaiha, SM., Lin, C., Lempert, LK., 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]

Participants in focus groups perceived oral nicotine pouches (ONPs) as having similar or lower risks compared to traditional cigarettes and smokeless tobacco, although they acknowledged potential gastrointestinal and cardiovascular risks.

ONPs were viewed as situational substitutes rather than complete replacements for cigarettes and smokeless tobacco, which could lead to increased overall nicotine use in certain populations, particularly in Appalachia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of oral nicotine pouches & their marketing among Ohio Appalachia smokers and smokeless tobacco users. Long, L., Alalwan, MA., Keller-Hamilton, B., et al.[2023]

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]

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]

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 significant portion of young adults, particularly those who currently use nicotine products, expressed a willingness to try oral nicotine pouches, with willingness rates of 33.8% for non-combustible users and 43.9% for dual users, compared to only 14.7% for non-users.

Despite this interest, many participants (49.1%) were uncertain about whether nicotine pouches are less harmful than cigarettes, indicating a lack of clear understanding regarding the safety of these products among young adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in Young Adults' Perceptions of and Willingness to Use Nicotine Pouches by Tobacco Use Status. Vogel, EA., Barrington-Trimis, JL., Kechter, A., et al.[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]

References

1. England pubmed.ncbi.nlm.nih.gov

Use, marketing, and appeal of oral nicotine products among adolescents, young adults, and adults. [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. United States pubmed.ncbi.nlm.nih.gov

Perceptions of oral nicotine pouches & their marketing among Ohio Appalachia smokers and smokeless tobacco users. [2023]

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

Nicotine delivery systems. [2015]

5. 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]

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Differences in Young Adults' Perceptions of and Willingness to Use Nicotine Pouches by Tobacco Use Status. [2023]

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

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