Nicotine Oral Pouches for Tobacco-Related Cancer Prevention

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University Comprehensive Cancer Center

Disqualifiers: Psychiatric conditions, Cardiac event, Pregnancy, Diabetes, 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

160 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must abstain from all tobacco, nicotine, and marijuana use for at least 12 hours before certain study visits.

What data supports the effectiveness of the drug Nicotine Oral Pouch for tobacco-related cancer prevention?

The research highlights the critical role of tobacco cessation in improving cancer treatment outcomes and survival, suggesting that reducing tobacco use can have positive effects on cancer prevention. While specific data on nicotine oral pouches is not provided, the general evidence supports the importance of tobacco cessation in cancer care. ^{1 2 3 4 5}

Is there any safety data available for nicotine oral pouches?

Current research on nicotine oral pouches suggests they may offer reduced harm compared to cigarettes, but there is limited independent data on their safety and potential misuse. More studies are needed to fully understand their safety profile. ^{6 7 8 9 10}

How do nicotine oral pouches differ from other treatments for tobacco-related cancer prevention?

Nicotine oral pouches are unique because they are tobacco-free and deliver nicotine by being placed between the lip and gum, unlike traditional smoking or chewing tobacco products. This method provides a smokeless and potentially less harmful way to consume nicotine, which may help in reducing the risk of tobacco-related cancers. ^{11 12 13 14 15}

What is the purpose of this trial?

This clinical trial evaluates the characteristics of oral nicotine pouches (ONPs) to determine if they are a comparable substitute to cigarette or smokeless tobacco (ST) products. ONPs contain nicotine but no tobacco and are used primarily by adult tobacco uses in the United States (US). ONPs are recognized by the Food and Drug Administration as having lower risk than combustible cigarettes and are approved as a modified risk tobacco product. While ONPs have lower toxic risk than other tobacco products, acute and longer term harm related to their use has not been studied. Information gathered from this study may identify product characteristics of ONPs that improve successful switching from high-risk cigarettes or ST to lower risk ONPs.

Research Team

Brittney L. Keller-Hamilton

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adult tobacco users in the US who are interested in switching from high-risk cigarettes or smokeless tobacco to oral nicotine pouches, which may have a lower toxic risk. The study aims to understand if these pouches can be an effective substitute.

Inclusion Criteria

Willing to provide informed consent and abstain from all tobacco, nicotine, and marijuana use for at least 12 hours prior to Phase 1 study visits

Willing to attend all study visits and use study ONPs

Owns a smartphone and able to receive short messaging service (SMS) text messages with embedded survey link (for daily diary reports of ONP and other tobacco use)

Exclusion Criteria

Unstable or significant psychiatric conditions (past and stable conditions will be allowed)

Currently pregnant, planning to become pregnant, or breastfeeding (will be verified with urine pregnancy test before each Phase 1 study visit [acute use of usual product and study ONPs] and Phase 2 study visit 1 [distribution of study ONPs for outpatient ad libitum use])

CIGARETTE SMOKERS ONLY: Roll-your-own cigarette smokers

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I

Participants are randomized to use one of the 4 study ONP products or their usual product brand of ST or cigarette. Blood samples are collected at various intervals.

Up to 3 months

5 visits (in-person)

Washout Period

Participants use their usual brand of ST or cigarettes for 1 week.

1 week

Control Week

Participants continue regular use of ST or cigarettes and receive daily diary surveys to record tobacco use.

1 week

Phase II Switch

Participants are randomized to switch to one of 4 study ONP products for 4 weeks. Oral mucosa samples are collected.

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

Treatment Details

Interventions

• Nicotine Oral Pouch

Trial Overview The study is examining oral nicotine pouches as potential substitutes for cigarettes or smokeless tobacco. Participants will use ONPs and receive text messages with guidance, complete surveys, and provide biospecimens to assess the effects and risks of ONPs.

Participant Groups

Group I: PHASE II ARM IV (high FBN > 99% ONP) Experimental Treatment 6 Interventions

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert high FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group II: PHASE II ARM III (high R/S ONP) Experimental Treatment 6 Interventions

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert to high R/S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group III: PHASE II ARM II (low FBN > 99% S ONP) Experimental Treatment 6 Interventions

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert to low FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group IV: PHASE II ARM I (low FBN R/S ONP) Experimental Treatment 6 Interventions

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert low FBN R/S ONP for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group V: PHASE I ARM V (Usual brand ST or cigarette) Experimental Treatment 4 Interventions

Participants insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

Group VI: PHASE I ARM IV (high FBN > 99% ONP) Experimental Treatment 5 Interventions

Participants insert high FBN \> 99% S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group VII: PHASE I ARM III (high FBN R/S ONP) Experimental Treatment 5 Interventions

Participants insert high R/S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group VIII: PHASE I ARM II (low FBN > 99% S ONP) Experimental Treatment 5 Interventions

Participants insert low FBN \> 99% S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group IX: PHASE I ARM I (low FBN R/S ONP) Experimental Treatment 5 Interventions

Participants insert low free-base nicotine (FBN) R/S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Tobacco use is a major preventable cause of cancer, linked to 30% of all cancer-related deaths in the U.S., and negatively impacts cancer treatment efficacy, quality of life, and survival outcomes.

The authors recommend that smoking history and status be systematically collected in all oncology clinical trials to better understand its effects on treatment outcomes and to improve patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking, the missing drug interaction in clinical trials: ignoring the obvious. Gritz, ER., Dresler, C., Sarna, L.[2015]

Nicotine treatment in SCC15 oral squamous cell carcinoma cells increased reactive oxygen species (ROS) levels and promoted cell growth, indicating a potential role in cancer cell proliferation.

At a concentration of 1 µmol/L, nicotine significantly increased cell apoptosis and activated the NF-κB signaling pathway, suggesting that nicotine may influence both growth and death of oral cancer cells through this mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of nicotine on the proliferation and cell apoptosis of oral squamous cell carcinoma SCC15 cells]. Zhang, M., Zhao, YH., Tang, XF., et al.[2018]

A significant number of patients with head and neck squamous cell carcinoma (HNSCC) continue to smoke after treatment, with 58.4% still smoking at 6 months and 44.9% at 24 months, indicating a persistent challenge in smoking cessation among this group.

The highest likelihood of quitting smoking occurred within the first 6 months post-treatment, suggesting that this period is critical for implementing effective smoking cessation interventions in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent Tobacco Use After Treatment for Head and Neck Cancer. Van Heest, T., Rubin, N., Khariwala, SS.[2023]

The Cancer Center Cessation Initiative (C3I) has successfully expanded access to tobacco cessation programs at 52 NCI-designated Cancer Centers, ensuring that cancer patients can receive evidence-based support for quitting tobacco.

Despite the increased availability of these services, patient utilization remains low, prompting the formation of the C3I Implementation Science Working Group to develop strategies that enhance the adoption of tobacco treatment interventions in oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation Science to Improve Tobacco Cessation Services in Oncology Care. [2022]

A study involving 246 clinicians and 2,146 cancer patients showed that electronic health record (EHR) nudges aimed at clinicians significantly increased tobacco use treatment (TUT) referrals and prescriptions, with TUT penetration rising from 13.5% in usual care to 35.6% with clinician nudges.

The results indicate that while clinician nudges were effective, adding patient nudges did not further enhance TUT engagement, suggesting that targeting clinicians may be the most effective strategy for improving tobacco treatment in oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cluster Randomized Pragmatic Clinical Trial Testing Behavioral Economic Implementation Strategies to Improve Tobacco Treatment for Patients With Cancer Who Smoke. Jenssen, BP., Schnoll, R., Beidas, RS., 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]

In a study involving 30 adult smokers, 6-mg oral nicotine pouches (ONPs) delivered more nicotine to the bloodstream at 30 minutes compared to both 3-mg ONPs and cigarettes, suggesting they can be effective for nicotine delivery.

However, neither concentration of ONPs provided as much relief from cravings at 5 minutes as cigarettes did, indicating that while ONPs may be less harmful, they might not satisfy cravings as effectively, which could influence their potential for misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study. Keller-Hamilton, B., Alalwan, MA., Curran, H., et al.[2023]

Approximately 46.6% of U.S. adult tobacco users are aware of nicotine pouches, but only 3.0% currently use them, indicating a gap between awareness and actual use.

Younger individuals and those who use smokeless tobacco are more likely to have used nicotine pouches, and having positive beliefs about NPs correlates with increased likelihood of use, highlighting the need for ongoing monitoring of public perceptions and usage trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine Pouch: Awareness, Beliefs, Use, and Susceptibility among Current Tobacco Users in the United States, 2021. Sparrock, LS., Phan, L., Chen-Sankey, J., et al.[2023]

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]

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]

The study analyzed nicotine pouch regulations across 67 countries, revealing significant differences in how these products are classified and regulated, particularly regarding synthetic nicotine.

Only 34 countries have regulations for nicotine pouches, with 23 of those including synthetic nicotine in their policies, highlighting a need for more consistent regulatory frameworks to ensure safety and control over these products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pouches: a summary of regulatory approaches across 67 countries. Duren, M., Atella, L., Welding, K., et al.[2023]

In a study involving 35 participants, the Lyft 10 mg nicotine pouch showed significantly higher nicotine absorption into the blood compared to combustible cigarettes, indicating that some nicotine pouches can deliver nicotine effectively.

While nicotine pouches can replicate nicotine uptake similar to cigarettes, users reported a lower preference and intent to reuse the pouches compared to cigarettes, suggesting differences in subjective satisfaction between the two products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette. McEwan, M., Azzopardi, D., Gale, N., et al.[2022]

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]

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

Smoking, the missing drug interaction in clinical trials: ignoring the obvious. [2015]

2. China pubmed.ncbi.nlm.nih.gov

[Effect of nicotine on the proliferation and cell apoptosis of oral squamous cell carcinoma SCC15 cells]. [2018]

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

Persistent Tobacco Use After Treatment for Head and Neck Cancer. [2023]

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

Implementation Science to Improve Tobacco Cessation Services in Oncology Care. [2022]

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

Cluster Randomized Pragmatic Clinical Trial Testing Behavioral Economic Implementation Strategies to Improve Tobacco Treatment for Patients With Cancer Who Smoke. [2023]

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

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotine Pouch: Awareness, Beliefs, Use, and Susceptibility among Current Tobacco Users in the United States, 2021. [2023]

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Nicotine pouches: a summary of regulatory approaches across 67 countries. [2023]

12. France pubmed.ncbi.nlm.nih.gov

A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette. [2022]

13. Canada pubmed.ncbi.nlm.nih.gov

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

14. England pubmed.ncbi.nlm.nih.gov

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

15. England pubmed.ncbi.nlm.nih.gov

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