Nicotine Pouches for Preventing Tobacco-Related Cancer

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: Chantix, Wellbutrin

Disqualifiers: Pregnancy, Cardiac events, Lung disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether nicotine pouches can help prevent tobacco-related cancers among residents in rural and Appalachian areas of Ohio. Participants will try different nicotine pouch brands and their usual smokeless tobacco to assess how these alternatives might affect health. The trial seeks individuals who have used smokeless tobacco daily for at least three months and are willing to abstain from all tobacco products for a short period before clinic visits. The study aims to determine if nicotine pouches could serve as a safer substitute for traditional smokeless tobacco. As an Early Phase 1 trial, this research focuses on understanding how nicotine pouches work in people, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must abstain from all tobacco, nicotine, and marijuana for 12 hours before clinic visits.

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

Research has shown that the FDA has thoroughly reviewed ZYN nicotine pouches and approved their marketing. This indicates they are generally well-tolerated. However, like any nicotine product, they can cause short-term side effects such as a faster heartbeat, irritation, and nausea. There is also a risk of allergic reactions, which can include swelling or trouble breathing.

Studies indicate that Rogue nicotine pouches can cause dizziness and headaches, especially in new users or those who use them excessively. They may also lead to oral health problems like gum disease and tooth loss.

Both products contain nicotine, which is addictive and can affect brain development in young people. The long-term health effects remain unknown, but current evidence suggests that the pouches are generally safe for adults when used as directed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nicotine pouches as a potential way to prevent tobacco-related cancer because they offer a smokeless alternative to traditional tobacco products. Unlike cigarettes or smokeless tobacco, which expose users to harmful carcinogens, nicotine pouches provide a cleaner delivery of nicotine without the combustion or direct contact with tobacco leaves. This new delivery method could significantly reduce the risk of cancer associated with tobacco use. Additionally, the variety of brands like ZYN and Rogue offer different formulations and flavors, potentially making it easier for users to transition away from more harmful tobacco products.

What evidence suggests that this trial's treatments could be effective for preventing tobacco-related cancer?

This trial will evaluate nicotine pouches, such as ZYN and Rogue, as alternatives to smokeless tobacco. Studies have shown that nicotine pouches are less harmful than smoking cigarettes. Research indicates that these pouches expose users to fewer cancer-causing chemicals and other toxic substances. The FDA found that nicotine pouches might help adults who smoke by providing nicotine with fewer harmful chemicals. ZYN and Rogue pouches deliver nicotine similarly to cigarettes but with potentially fewer risks. This suggests they could be a safer option for those trying to lower their risk of tobacco-related cancer. Participants in this trial will receive different sequences of ZYN and Rogue nicotine pouches along with their usual smokeless tobacco to assess these potential benefits. ^{1 6 7 8 9}

Who Is on the Research Team?

Brittney L. Keller-Hamilton

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 21 who live in Ohio Appalachia or nearby rural areas, use smokeless tobacco daily, and can abstain from all tobacco, nicotine, and marijuana before clinic visits. It's not for those with certain lung diseases, oral cancers, recent heart issues, pregnant/breastfeeding women, people planning to quit tobacco soon or using cessation aids.

Inclusion Criteria

Reside in an Ohio Appalachian county or surrounding rural area

Willing to complete study procedures, including abstaining from all tobacco, nicotine, and marijuana for 12 hours before clinic visits

Daily use of smokeless tobacco for the past 3 months

Exclusion Criteria

I have not had heart problems, uncontrolled high blood pressure, significant mouth issues, or severe shortness of breath in the last year.

Use tobacco products other than smokeless tobacco more than 10 days per month

Unstable or significant psychiatric conditions for more than 1 year (past and stable conditions will be allowed)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive different brands of nicotine pouches and their usual smokeless tobacco over three study visits, with blood collection and IV line insertion

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Oral Pouch
• Smokeless Tobacco

Trial Overview The study looks at the impact of nicotine pouches as a substitute for smokeless tobacco among residents of rural Ohio. Participants will collect biospecimens and answer questionnaires to help researchers understand how these products are adopted and their public health implications.

How Is the Trial Designed?

Group I: Arm VI (Rogue NP, ZYN NP, usual SLT) Experimental Treatment 4 Interventions

Participants receive Rogue brand nicotine patch at study visit 1, ZYN brand nicotine patch at study visit 2, and their usual brand of smokeless tobacco at study visit 3. Participants also undergo IV line insertion and collection of blood on study

Group II: Arm V (Rogue NP, usual SLT, ZYN NP) Experimental Treatment 4 Interventions

Participants receive Rogue brand nicotine patch at study visit 1, their usual brand of smokeless tobacco at study visit 2, and ZYN brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study.

Group III: Arm IV (ZYN NP, Rogue NP, usual SLT) Experimental Treatment 4 Interventions

Participants receive ZYN brand nicotine patch at study visit 1, Rogue brand nicotine patch at study visit 2, and their usual brand of smokeless tobacco at study visit 3. Participants also undergo IV line insertion and collection of blood on study.

Group IV: Arm III (ZYN NP, usual SLT, Rogue NP) Experimental Treatment 4 Interventions

Participants receive ZYN brand nicotine patch at study visit 1, their usual brand of smokeless tobacco at study visit 2, and Rogue brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study.

Group V: Arm II (usual SLT, Rogue NP, ZYN NP) Experimental Treatment 4 Interventions

Participants receive their usual brand of smokeless tobacco at study visit 1, Rogue brand nicotine patch at study visit 2, and ZYN brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study.

Group VI: Arm I (usual SLT, ZYN NP, Rogue NP) Experimental Treatment 4 Interventions

Participants receive their usual brand of smokeless tobacco at study visit 1, ZYN brand nicotine patch at study visit 2, and Rogue brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11931220/

The Potential Impact of Oral Nicotine Pouches on Public ... ONPs appear to be less toxic than cigarettes and deliver comparable nicotine, presenting an alternative for combustible product users.

2. withpower.com withpower.com/trial/early-phase-1-tobacco-related-carcinoma-3-2023-dea60

Nicotine Pouches for Preventing Tobacco-Related Cancer Research suggests that nicotine pouches may expose users to fewer harmful substances compared to smoking cigarettes, indicating a potentially safer profile.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12417499/

Nicotine pouches: a narrative review of the existing literature The FDA determined that these tobacco-free products pose a lower risk of cancer and other serious health conditions than combustible tobacco, ...

4. cureus.com cureus.com/articles/224004-tobacco-free-nicotine-pouches-and-their-potential-contribution-to-tobacco-harm-reduction-a-scoping-review

Tobacco-Free Nicotine Pouches and Their Potential ... Overall, studies examining chemical constituents indicated that the use of TFNPs may result in lower exposure to toxicants than other tobacco or ...

5. mdanderson.org mdanderson.org/cancerwise/what-to-know-about-nicotine-pouches.h00-159773289.html

What to know about nicotine pouches One study found that smoking one cigarette resulted in 11.4 nanograms per milliliter of nicotine in the blood after 30 minutes, while using one ...

6. webmd.com webmd.com/smoking-cessation/nicotine-pouches

Nicotine Pouches: Use, Benefits, and Risks Nicotine Pouch Side Effects · Cancers of the mouth, throat, and pancreas · Gum disease · Tooth loss · Cavities and stained teeth · Higher chances of ...

7. bfr.bund.de bfr.bund.de/cm/349/health-risk-assessment-of-nicotine-pouches.pdf

Health risk assessment of nicotine pouches The scores given to the side effects of drowsiness, pounding heart, headache, throat irritation, sweating, dizziness, cold hands and feet, ...

8. nicobolt.com nicobolt.com/rogue-nicotine-pouches-side-effects-what-you-need-to-know/?srsltid=AfmBOoqKhFl3luJFt5_nzkJ2NxJjbpyTxVa7E1QnYTA5IaHDrPV3JmA9

Rogue Nicotine Pouches Side Effects Dizziness: New users or those who exceed their tolerance level may feel lightheaded or unsteady. Headaches: Nicotine-induced dehydration or overstimulation can ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9985244/

Harmful and potentially harmful constituents (HPHCs) in ... The two ZYN products contained no nitrosamines or polycyclic aromatic hydrocarbons (PAHs) but low levels of ammonia, chromium, formaldehyde, and nickel.