Nicotine Pouches for Smoking Cessation

(Pack2Pouch Trial)

Recruiting at 1 trial location

Overseen By Talia Ogretman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Smoking cessation medications

Disqualifiers: Non-cigarette tobacco, Marijuana, 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: 3

Duration: 4 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nicotine pouches can help people quit smoking cigarettes. It compares two different strengths of nicotine pouches to determine which is more effective in encouraging people to switch from smoking. Participants will use nicotine pouches for four weeks and provide feedback about their tobacco habits. The trial suits those who smoke regularly and can attend two visits in Charleston. As an unphased trial, it offers an opportunity to contribute to research that could help many people quit smoking.

Will I have to stop taking my current medications?

If you are currently using smoking cessation medications like varenicline, bupropion, or nicotine replacement therapy, you will need to stop taking them to participate in this trial.

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

Research has shown that nicotine pouches might help some people smoke less or quit smoking. However, their safety remains under investigation. One study found that while these pouches helped people smoke fewer cigarettes, they did not reduce the harmful effects of tobacco exposure. The FDA has not approved nicotine pouches for quitting smoking, and researchers continue to study their effects. Some individuals have reported quitting successfully using these pouches, but there is no clear evidence that they lower health risks. Nicotine is addictive, so weighing the pros and cons before trying these pouches is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Nicotine pouches for smoking cessation are exciting because they offer a smoke-free and convenient option compared to traditional methods like nicotine patches, gum, or lozenges. Unlike these methods, nicotine pouches come in different dosages, such as high (6mg) and low (3mg), allowing for customizable nicotine intake. These pouches are discreet and don't require chewing or sticking to the skin, providing a more socially acceptable way to manage cravings. Researchers are particularly interested in how these pouches might appeal to smokers seeking a flexible and less intrusive way to quit.

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

Studies have shown that nicotine pouches can help people reduce or quit smoking. Research indicates that these pouches significantly reduce the urge to smoke. In one study, participants who used nicotine pouches were more likely to stop smoking than those who did not. This trial will compare different strengths of nicotine pouches, with one group receiving a high dosage (6mg) and another group receiving a low dosage (3mg). Both strengths have proven effective in helping people smoke less. By providing nicotine without the harmful chemicals found in cigarettes, these pouches offer a safer way to manage nicotine addiction.

Who Is on the Research Team?

Amanda Palmer

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for individuals who are currently cigarette smokers and want to switch to a less harmful alternative. Participants will be asked to use tobacco-free nicotine pouches with varying nicotine levels over 4 weeks, provide breath and cheek swab samples, and answer questions about their tobacco use.

Inclusion Criteria

I have used TNF blockers less than 5 times in my life.

Have internet access

I can go to Charleston for 2 visits to check my health markers.

Exclusion Criteria

Lack of proficiency in English

Use of marijuana within the past month, and unwillingness to abstain from marijuana during the course of the study

I have used tobacco products or e-cigarettes in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a 28-day supply of nicotine pouches and are asked to switch from smoking to pouches over 4 weeks

4 weeks

1 visit (in-person), daily surveys

Follow-up

Participants are monitored for smoking reduction and switching to nicotine pouches

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Pouches

Trial Overview The study is testing the effectiveness of low versus high nicotine dose in tobacco-free oral nicotine pouches at helping cigarette smokers switch away from smoking. It involves an initial visit, a month-long period using the provided pouches, followed by a final visit and additional follow-up.

How Is the Trial Designed?

Group I: Low Nicotine Experimental Treatment 1 Intervention

Low dosage nicotine pouches (3mg)

Group II: High Nicotine Experimental Treatment 1 Intervention

High dosage nicotine pouches (6mg)

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?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

In a study of 30 adult smokers, the 4-mg nicotine pouch significantly reduced withdrawal cravings by 23 points within the first hour, outperforming nicotine gum and placebo, which showed reductions of 15 and 8 points, respectively.

Participants rated the nicotine pouch as more helpful and pleasant to use compared to gum, indicating a preference that could enhance its effectiveness as a smoking cessation aid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-blind, randomized, crossover trial of the effects of a nicotine pouch on the relief of tobacco withdrawal symptoms and user satisfaction. Thornley, S., McRobbie, H., Lin, RB., 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12377922/

The Effects of Oral Nicotine Pouches on Cigarette Smoking ... Though oral nicotine pouches significantly reduced cigarette smoking over 4 weeks, they did not decrease tobacco-related harm exposure, likely ...

2. cdc.gov cdc.gov/tobacco/nicotine-pouches/index.html

Nicotine Pouches | Smoking and Tobacco Use The FDA has not approved any nicotine pouches to help people quit smoking. Researchers need more information to understand the potential effects ...

3. nature.com nature.com/articles/s41598-025-15070-0

Prevalence, safety, and role of nicotine pouches in ... Among those who had used nicotine pouches, 41.0% reported success in quitting smoking, while 38.1% experienced partial success, and 20.9% were ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.70193?af=R

Nicotine pouches and clinical outcomes related to smoking ... First, while a 2-week crossover study showed that NPs reduced the number of cigarettes smoked, this reduction was similar to that achieved with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2214750024001628

Beyond smoking: Risk assessment of nicotine in pouches This study aims to assess nicotine in pouches and potential risks for health damage. 31 samples of nicotine pouches were collected and analyzed.