Oral Nicotine Pouches Versus Nicotine Replacement Therapy to Reduce Cigarette Use for Smokers in Rural Appalachia (ARISE)

Testing Oral Nicotine Pouches to Reduce Smoking-Related Cancer in Rural Appalachia

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.

Study Overview

• Status: Recruiting
• Conditions: Cigarette Smoking-Related Carcinoma
• Intervention / Treatment: Other: Carbon Monoxide Measurement; Other: Oral Nicotine Pouch; Other: Survey Administration; Other: Check-in Phone Calls; Other: Nicotine Lozenge; Other: Nicotine Patch

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate short-term changes in cigarette smoking patterns, including switching, abstinence from cigarettes, and frequency of smoking between oral nicotine patches (ONPs) and NRT.

II. Compare product appeal, craving, withdrawal relief, and perceived cigarette dependence between ONPs and NRT.

III. Examine sustained changes in tobacco use behaviors, including abstinence from cigarettes, purchase of ONPs/NRT, and continued use of ONPs/NRT.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I:

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.

ARM II:

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.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Principal Investigator: Brittney L. Keller-Hamilton
      • Contact: Brittney L. Keller-Hamilton, PhD, MPH; Phone Number: 614-366-9652

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Read and speak English
• 21 years or older
• Smoke ≥ 5 cigarettes per day for the past year
• Willing to use Oral Nicotine Pouches (ONP) or Nicotine Replacement Therapy (NRT)
• Live in a rural Appalachian County
• Have a smartphone and/or willing to use a smartphone for study purposes (smartphones may be provided to participants for study purposes only)
• Willing to blow air into a handheld study device
• If capable of becoming pregnant, verbal confirmation of not being pregnant based on urine pregnancy test results

Exclusion Criteria:

• Report currently using smoking cessation medications, NRT, or actively seeking treatment for smoking cessation
• Use of ONPs in past 3 months
• Use of Nicotine Replacement Therapies in past 3 months
• Use of other tobacco products > 10 days/month
• Unstable or significant medical condition
• Unstable or significant psychiatric conditions (past and stable conditions will be allowed)
• History of cardiac event or distress within the past 3 months
• Live in same household as another study participant.
• Currently pregnant, planning to become pregnant within 6 months, or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (oral nicotine pouch); 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.	Other: Carbon Monoxide Measurement; Undergo carbon monoxide measurement; Other Names: Carbon Monoxide; Covita iCOquit; Other: Oral Nicotine Pouch; Use oral nicotine pouch; Other Names: ZYN; Other: Survey Administration; measurements; data gathering; Other: Check-in Phone Calls; Check-in phone calls to study participants
Active Comparator: Arm II (nicotine replacement therapy); 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.	Other: Carbon Monoxide Measurement; Undergo carbon monoxide measurement; Other Names: Carbon Monoxide; Covita iCOquit; Other: Survey Administration; measurements; data gathering; Other: Check-in Phone Calls; Check-in phone calls to study participants; Other: Nicotine Lozenge; Use nicotine lozenge; Other Names: Nicotine Replacement Therapy; Rugby; Other: Nicotine Patch; Use nicotine patch; Other Names: Nicotine Replacement Therapy; Nicotine Skin Patch; Nicotine Transdermal Patch; Rugby

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemically verified 7-day point prevalence abstinence from cigarettes	Statistical analyses will be performed using SAS 9.4. P-values less than 0.05 will be considered statistically significant. Will be presented as frequencies and proportions and compared with chi-squared tests.	At the end of the 12- week switch phase
Complete switching rate (Aim 1)	Will be compared between arms using logistic regression analysis, adjusting for baseline variables as needed.	At the end of the 12-week switch phase
Abstinence from cigarettes (Aim 1)	Will be compared between arms using logistic regression analysis, adjusting for baseline variables as needed.	At the end of the 12-week switch phase
Cigarettes smoked per day (Aim 1)	If needed, will apply a normalizing transformation to the number of cigarettes smoked per day (e.g., taking the logarithm) before proceeding with the analysis as a means of removing the effects of potential outliers. Will compare cigarettes smoked per day between the two arms using linear regression analysis. The model will adjust for cigarettes smoked per day at baseline and other baseline variables if they are imbalanced.	At the end of the 12-week switch phase
Differences in product appeal (Aim 2)	Will be adjusted for potential confounders including baseline variables such as age, gender, number of cigarettes smoked per day, and/or randomization stratification factors as necessary; normalizing transformations will be employed if needed.	From baseline to the end of the 12 week switch phase
Cigarette craving (Aim 2)	Will be evaluated with linear regression models adjusting for appropriate confounders.	Up to the end of the 12 week switch phase
Withdrawal symptoms (Aim 2)	Will be evaluated with linear regression models adjusting for appropriate confounders.	Up to the end of the 12 week switch phase
Change in nicotine dependence among participants who completely switched to their assigned study product (Aim 2)	Using linear regression analysis, adjusting for baseline nicotine dependence.	From baseline to the end of the 12 weeks switch phase
Abstinence from cigarettes (Aim 3)	Will be compared between arms using logistic regression analysis and will be evaluated with a logistic regression model.	Up to the end of the 14 week observation phase
Number of days the study products are used (Aim 3)	Linear regression analysis will be used to compare the number of days the products are used. A normalizing transformation will be employed if needed and appropriate baseline characteristics will be adjusted for.	Up to the end of the 14 week observation phase
Purchase and continued use of the study products (Aim 3)	Will be compared between the arms with logistic regression analysis, adjusting for all appropriate confounders.	Up to the end of the 14 week observation phase

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Brittney L Keller-Hamilton, PhD, MPH, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 2, 2025
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Actual): June 22, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antimetabolites; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Gasotransmitters; Nicotine; Carbon Monoxide
• Other Study ID Numbers: 2024C0064; NCI-2024-09181 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA289551-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No