Oral Nicotine Pouches for Tobacco Use Disorder

Overseen by Tory Spindle, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive drugs, OTC drugs

Disqualifiers: Significant medical condition, psychiatric condition, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies how healthy adult smokers respond to tobacco-free oral nicotine pouches. The pouches come in various flavors and strengths, and the study measures how the body absorbs and reacts to the nicotine, including effects on withdrawal symptoms and vital signs. Tobacco-free oral nicotine pouch products have emerged as a potential reduced risk product compared with cigarettes and other tobacco products.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications if they impact safety, as determined by the investigators or medical staff. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of oral nicotine pouches as a treatment for tobacco use disorder?

Research suggests that oral nicotine pouches, like Velo, expose users to fewer harmful chemicals compared to smoking cigarettes, and they may help reduce withdrawal symptoms and provide user satisfaction similar to or better than nicotine gum or lozenges. This indicates they could be a safer and more satisfying alternative for those trying to quit smoking. ^{1 2 3 4 5}

Are oral nicotine pouches safe for humans?

Research suggests that oral nicotine pouches, like Velo and ZYN, expose users to fewer harmful chemicals compared to smoking cigarettes, making them a potentially safer alternative. However, there is limited research on their long-term safety, and they are still being studied to fully understand their health effects. ^{1 2 6 7 8}

How do oral nicotine pouches differ from other treatments for tobacco use disorder?

Oral nicotine pouches are unique because they are tobacco-free and provide nicotine through a smokeless, discreet method, potentially reducing exposure to harmful tobacco-related chemicals compared to traditional tobacco products like cigarettes or snus. ^{1 2 7 9 10}

Research Team

Tory Spindle, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for healthy adult smokers who smoke daily, have a mild tobacco use disorder, and haven't used other tobacco products or nicotine pouches recently. They must be over 21 years old with normal vital signs and no recent drug use (except THC). Pregnant women, those in another trial within the last month, or using certain medications are excluded.

Inclusion Criteria

Self-report currently smoking daily

Good general health based on screening procedures (e.g., physical exam, blood testing)

No self-reported regular use of other tobacco products (e.g., smokeless products, e-cigarettes) in the past 30 days

Exclusion Criteria

Enrollment in another clinical trial in the past 30 days

History of or current significant medical condition that, in the opinion of the investigators or medical staff, will impact safety

I am not taking any medications or supplements that could affect my safety in the trial.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete 7 dosing conditions with various nicotine pouches and cigarettes, including controlled and ad libitum use

7 sessions (each separated by at least 48 hours)

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cigarette (Smoking Cessation Aid)
• Nicotine (Nicotine Replacement Therapy)

Trial Overview The study tests 'tobacco-free' oral nicotine pouches of different flavors and doses against regular cigarettes to see how they affect the body and cravings. Participants will try each product under controlled conditions first, then freely for two hours in a double-blind setup.

Participant Groups

Group I: Original/Tobacco Flavored Pouch (low nicotine dose) Experimental Treatment 1 Intervention

participants will use a tobacco flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Group II: Original/Tobacco Flavored Pouch (high nicotine dose) Experimental Treatment 1 Intervention

participants will use a tobacco flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Group III: Mint/Menthol Flavored Pouch (low nicotine dose) Experimental Treatment 1 Intervention

participants will use a mint/menthol flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Group IV: Mint/Menthol Flavored Pouch (high nicotine dose) Experimental Treatment 1 Intervention

participants will use a mint/menthol flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Group V: Fruit Flavored Pouch (low nicotine dose) Experimental Treatment 1 Intervention

participants will use a fruit flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Group VI: Fruit Flavored Pouch (high nicotine dose) Experimental Treatment 1 Intervention

participants will use a fruit flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Group VII: Own brand cigarettes Active Control 1 Intervention

participants will smoke participants' own brand of cigarettes under both controlled (experimenter-directed) and ad libitum use conditions

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

Exclusive users of Velo nicotine pouches showed significantly lower levels of harmful biomarkers compared to smokers, including a 91% reduction in total NNAL and a 46% reduction in carbon monoxide levels, indicating a lower risk of smoking-related diseases.

Velo users had higher total nicotine equivalents than smokers, but overall exposure to tobacco toxicants was much lower, suggesting that Velo pouches may be a safer alternative for nicotine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Azzopardi, D., Haswell, LE., Frosina, J., et al.[2023]

In a study involving 34 healthy adult smokers, tobacco-free oral nicotine pouches (NPs) showed similar nicotine absorption to lozenges and significantly better absorption than gum, indicating they may be an effective alternative for nicotine delivery.

Participants reported higher satisfaction with NPs compared to lozenges, and NPs had a lower incidence of minor adverse events, suggesting they are a well-tolerated option for smokers seeking nicotine replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised study to assess the nicotine pharmacokinetics of an oral nicotine pouch and two nicotine replacement therapy products. Azzopardi, D., Ebajemito, J., McEwan, M., et al.[2022]

Adult tobacco users perceive oral nicotine pouches (ONPs) as significantly less harmful and less addictive compared to non-users, indicating a potential misperception of risk among users.

The displayed nicotine concentration on ONP packaging significantly influences perceptions of harm and addictiveness, with higher concentrations leading to lower perceived risks, suggesting that packaging features could impact public health perceptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Oral Nicotine Pouch Packaging Features on Adult Tobacco Users' and Non-Users' Product Perceptions. Mays, D., Long, L., Alalwan, MA., 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]

In a study of 609 young adults aged 18-25, 41.5% reported awareness of nicotine pouches (NPs), with 10.3% having used them, indicating a growing interest in this tobacco-free nicotine product.

Young adults showed uncertainty about the risks and benefits of NPs compared to smokeless tobacco, but those who were susceptible or had used NPs had more favorable perceptions, suggesting that positive views on NPs may drive their use among this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Awareness, susceptibility, and use of oral nicotine pouches and comparative risk perceptions with smokeless tobacco among young adults in the United States. Morean, ME., Bold, KW., Davis, DR., et al.[2023]

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]

References

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

Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. [2023]

2. 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]

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

A randomised study to assess the nicotine pharmacokinetics of an oral nicotine pouch and two nicotine replacement therapy products. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Oral Nicotine Pouch Packaging Features on Adult Tobacco Users' and Non-Users' Product Perceptions. [2023]

5. England 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. [2015]

6. England pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? [2023]

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. United States pubmed.ncbi.nlm.nih.gov

Awareness, susceptibility, and use of oral nicotine pouches and comparative risk perceptions with smokeless tobacco among young adults in the United States. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Nicotine delivery systems. [2015]

10. Canada pubmed.ncbi.nlm.nih.gov

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