Nicotine Pouches vs Replacement Therapy for Cancer Risk Reduction

(ARISE Trial)

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: Smoking cessation medications

Disqualifiers: Unstable medical, psychiatric conditions, others

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

Compensation: Varies

Number of Visits: 2

1000 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using smoking cessation medications or nicotine replacement therapies.

What data supports the effectiveness of the treatment Nicotine Replacement Therapy and Oral Nicotine Pouches for cancer risk reduction?

Research shows that oral nicotine pouches may provide a more satisfying alternative to traditional nicotine replacement therapies like gum and lozenges, with similar nicotine delivery and fewer minor side effects. Additionally, comprehensive tobacco treatment, which includes nicotine replacement therapies, can improve health outcomes and increase success in quitting smoking, which is a major risk factor for cancer. ^{1 2 3 4 5}

Is it safe to use nicotine pouches and nicotine replacement therapies?

Research suggests that oral nicotine pouches and nicotine replacement therapies are generally well-tolerated in humans, with minor adverse events reported less frequently for pouches compared to other forms like lozenges and gum. ^{1 2 6 7 8}

How do oral nicotine pouches differ from nicotine replacement therapy for cancer risk reduction?

Oral nicotine pouches are a newer, tobacco-free product that delivers nicotine through the mouth and may offer a more satisfying alternative to traditional nicotine replacement therapies like gum or lozenges. They provide similar nicotine levels but with potentially fewer minor side effects and greater user satisfaction. ^{1 2 9 10 11}

What is the purpose of this trial?

This clinical trial compares the use of oral nicotine pouches to nicotine replacement therapy, consisting of nicotine patches and lozenges, to reduce cigarette use in smokers living in rural Appalachia. The lung and oral cancers that plague Appalachia are fueled by cigarette smoking. Oral nicotine pouches which contain nicotine but no tobacco leaf, present a new opportunity to reduce cancer risk among Appalachian adults who smoke. Oral nicotine pouches and nicotine replacement therapy may work well to reduce cigarette use for smokers in rural Appalachia.

Research Team

Brittney L Keller-Hamilton, PhD, MPH

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for smokers in rural Appalachia who are interested in reducing cigarette use. Participants should be willing to try oral nicotine pouches or nicotine replacement therapy (patches and lozenges) and complete surveys and carbon monoxide measurements.

Inclusion Criteria

I have a smartphone or am willing to use one for the study.

Smoke ≥ 5 cigarettes per day for the past year

Willing to use and report at least minimal interest in switching to ONPs or NRT (> 'not at all' on a Likert scale)

Exclusion Criteria

I am currently using or seeking help to quit smoking.

Use of other tobacco products > 10 days/month

I do not have any major health issues that are not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sampling

Participants receive different concentrations and flavors of nicotine products to determine their preferred choice

2 weeks

1 visit (in-person)

Switch

Participants use their preferred nicotine products in place of cigarettes

12 weeks

Multiple visits (in-person) for surveys and carbon monoxide measurements

Observation

Participants complete a final follow-up survey and carbon monoxide measure

14 weeks

1 visit (in-person)

Follow-up

Participants are monitored for sustained changes in tobacco use behaviors

4 weeks

Treatment Details

Interventions

• Nicotine Replacement Therapy
• Oral Nicotine Pouches

Trial Overview The study compares oral nicotine pouches with traditional nicotine replacement therapies like patches and lozenges. The goal is to see which method better helps reduce cigarette smoking, potentially lowering cancer risks among participants.

Participant Groups

Group I: Arm I (oral nicotine pouch) Experimental Treatment 4 Interventions

SAMPLING PHASE: Participants receive 2 concentrations of three different flavors of oral nicotine pouches. Participants use the products ad libitum, starting with the lowest concentration, to determine their preferred concentration and flavor, over 2 weeks. SWITCH PHASE: Participants receive their preferred oral nicotine pouches and use them in place of cigarettes for 12 weeks. Participants complete surveys and have their carbon monoxide levels measured at various points throughout the study. OBSERVATION PHASE: After completion of the intervention, participants complete a final follow-up survey, along with a carbon monoxide measure, 14 weeks after the intervention ends.

Group II: Arm II (nicotine replacement therapy) Active Control 5 Interventions

SAMPLING PHASE: Participants receive 2 different strengths of nicotine replacement therapy patches and 2 different strengths and 3 different flavors of nicotine replacement therapy lozenges. Participants use the products ad libitum, starting with the lowest concentration, to determine their preferred concentration and flavor, over 2 weeks. SWITCH PHASE: Participants receive their preferred nicotine patches and lozenges and use them in place of cigarettes for 12 weeks. Participants complete surveys and have their carbon monoxide levels measured at various points throughout the study. OBSERVATION PHASE: After completion of intervention, participants complete a final follow-up survey, along with a carbon monoxide measure, 14 weeks after the intervention ends.

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

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]

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]

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]

Participants receiving an 8-week nicotine replacement therapy (NRT) had significantly higher quit rates (42.5%) compared to those receiving a 4-week NRT (33.3%), indicating that longer NRT duration enhances cessation success.

Among participants in a multiple-call program, those who received both 4-week NRT shipments had a quit rate of 51.1%, compared to 31.1% for those who only received one shipment, suggesting that consistent support and extended NRT can improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of a Temporary NRT Enhancement in a State Quitline and Web-Based Program. Cole, S., Suter, C., Nash, C., et al.[2019]

Tobacco use is a significant risk factor for cancer and negatively impacts cancer prognosis, yet effective cessation treatments are underutilized in oncology settings.

Implementing a comprehensive tobacco treatment program, which includes automatic referrals, motivational interviewing, and combined behavioral and pharmacological interventions, can significantly enhance smoking cessation success and improve health outcomes for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobacco Cessation in Oncology Care. Kaiser, EG., Prochaska, JJ., Kendra, MS.[2023]

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]

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]

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]

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]

In a study of 84,667 patients in a smoking cessation program, it was found that the prescribed doses of nicotine replacement therapy (NRT) did not increase adequately with the number of cigarettes smoked per day, leading to potential under-treatment.

Patients who received initial NRT doses below 2 mg per cigarette per day had poorer cessation outcomes, suggesting that higher doses may be necessary for heavy smokers to improve their chances of quitting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adequacy of nicotine replacement and success quitting tobacco in clinical populations: An observational study. Veldhuizen, S., Behal, A., Zawertailo, L., et al.[2023]

References

1. 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]

2. 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]

3. 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]

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

Impact of a Temporary NRT Enhancement in a State Quitline and Web-Based Program. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Tobacco Cessation in Oncology Care. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

8. France pubmed.ncbi.nlm.nih.gov

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

9. Canada pubmed.ncbi.nlm.nih.gov

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

10. 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]

11. Ireland pubmed.ncbi.nlm.nih.gov

Adequacy of nicotine replacement and success quitting tobacco in clinical populations: An observational study. [2023]