Appeal of Nicotine Pouches Versus Cigarettes in the Ohio Appalachia Population

Examining the Appeal of Nicotine Pouches in Ohio Appalachia

This clinical trial estimates the abuse liability of nicotine pouches with varying nicotine concentrations relative to cigarette smoking in Appalachian, Ohio and Ohio smokers. Nicotine pouches are a novel tobacco product with potential to reduce or increase the harm of tobacco use. Evaluating nicotine pouches abuse liability among smokers in Ohio including the unique demographic of Appalachia may clarify the public health effect of NPs in Appalachian Ohio and across Ohio. Results may inform public health efforts, policy, and clinical care aimed at reducing tobacco-related disparities.

Study Overview

• Status: Completed
• Conditions: Cigarette Smoking-Related Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Drug: Nicotine Oral Pouch; Drug: Nicotine Oral Pouch; Drug: Nicotine Oral Pouch; Behavioral: Cigarette Smoking

Detailed Description

Aim 1:

PRIMARY OBJECTIVE:

I. To estimate the abuse liability of nicotine pouches (NPs) with varying nicotine concentrations relative to cigarette smoking.

SECONDARY OBJECTIVE:

I. To clarify the public health effect of NPs in Appalachian Ohio.

EXPLORATORY OBJECTIVES:

I. To estimate the abuse liability of NPs with varying nicotine concentrations relative to cigarette smoking by measuring nicotine pharmacokinetics.

II. To estimate the abuse liability of NPs with varying nicotine concentrations relative to cigarette smoking by measuring subjective effects.

III. To estimate the abuse liability of NPs with varying nicotine concentrations relative to cigarette smoking by measuring intentions to use and switch to NPs.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive lower dose nicotine pouch orally (PO) over 30 minutes at visits 1, 2, and 3.

ARM II: Patients receive higher dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3.

ARM III: Patients smoke usual brand of cigarettes, taking one puff every 30 seconds over 5 minutes at visits 1, 2, and 3.

Aim 2:

PRIMARY OBJECTIVE:

I. To understand the pharmacokinetic difference between tobacco-derived and synthetic NPs.

SECONDARY OBJECTIVE:

I. To clarify the public health effect of NPs on adult smokers

EXPLORATORY OBJECTIVES:

I. To understand the differences in abuse liability between tobacco-derived and synthetic NPs by measuring nicotine pharmacokinetics.

II. To understand the differences in abuse liability between tobacco-derived and synthetic NPs by measuring subjective effects.

III. To estimate the abuse liability of tobacco-derived vs. synthetic NPs by measuring intentions to use and switch to NPs.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive a 3mg dose nicotine pouch orally (PO) over 30 minutes at visits 1, 2, and 3.

ARM II: Patients receive a 3mg dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3.

ARM III: Patients receive a 3mg dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Aim 1 Inclusion Criteria:

• Age 21 years or older.
• Reside in an Ohio Appalachian county.
• Willing to complete study procedures, including abstaining from all tobacco, nicotine, and marijuana for 12 hours before clinic visits.
• Ability to read and speak English.
• Smoke at least 5 cigarettes per day for the past 30 days.

Exclusion Criteria:

• Use tobacco products other than cigarettes >10 days per month.
• Use NP in the past 3 months.
• Unstable or significant psychiatric conditions (past and stable conditions will be allowed).
• Pregnant, planning to become pregnant, or breastfeeding.
• History of cardiac event or distress within the past 3 months.
• Currently attempting to quit all tobacco use.
• Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, or chronic obstructive pulmonary disease.

Aim 2 Inclusion Criteria:

• Age 21 years or older.
• Reside in a Ohio.
• Willing to complete study procedures, including abstaining from all tobacco, nicotine, and marijuana for 12 hours before clinic visits.
• Ability to read and speak English.
• Smoke at least 5 cigarettes per day for the past 30 days.

Exclusion Criteria:

• Use tobacco products other than cigarettes >10 days per month.
• Use NP in the past 3 months.
• Unstable or significant psychiatric conditions (past and stable conditions will be allowed).
• Pregnant, planning to become pregnant, or breastfeeding.
• History of cardiac event or distress within the past 3 months.
• Currently attempting to quit all tobacco use.
• Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, or chronic obstructive pulmonary disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aim 1: Arm I (lower dose nicotine pouch); Patients receive lower dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3.	Other: Questionnaire Administration; Ancillary studies; Drug: Nicotine Oral Pouch; Given lower dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given higher dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given 3mg nicotine pouch (Aim 2); Other Names: Fre
Experimental: Aim 1: Arm II (higher dose nicotine pouches); Patients receive higher dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3.	Other: Questionnaire Administration; Ancillary studies; Drug: Nicotine Oral Pouch; Given lower dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given higher dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given 3mg nicotine pouch (Aim 2); Other Names: Fre
Active Comparator: Aim 1: Arm III (cigarette smoking); Patients smoke usual brand of cigarettes, taking one puff every 30 seconds over 5 minutes at visits 1, 2, and 3.	Other: Questionnaire Administration; Ancillary studies; Behavioral: Cigarette Smoking; Smoke preferred brand of cigarette
Experimental: Aim 2: Arm I (3mg NP); Patients receive nicotine pouch PO over 30 minutes at visits 1, 2, and 3.	Other: Questionnaire Administration; Ancillary studies; Drug: Nicotine Oral Pouch; Given lower dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given higher dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given 3mg nicotine pouch (Aim 2); Other Names: Fre
Experimental: Aim 2: Arm II (3mg NP); Patients receive nicotine pouch PO over 30 minutes at visits 1, 2, and 3.	Other: Questionnaire Administration; Ancillary studies; Drug: Nicotine Oral Pouch; Given lower dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given higher dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given 3mg nicotine pouch (Aim 2); Other Names: Fre
Experimental: Aim 2: Arm III (3mg NP); Patients receive nicotine pouch PO over 30 minutes at visits 1, 2, and 3.	Other: Questionnaire Administration; Ancillary studies; Drug: Nicotine Oral Pouch; Given lower dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given higher dose nicotine pouch; Other Names: ZYN; Drug: Nicotine Oral Pouch; Given 3mg nicotine pouch (Aim 2); Other Names: Fre

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate plasma nicotine concentration at t=30 minutes for each product.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1: Public health effect of NPs in Appalachian Ohio - if NPs can be used as a substitute for cigarette smoking	Data collected will show if NPs are a viable substitute for cigarette smoking.	Up to 6 months
Evaluate plasma nicotine concentrations at t=5 through t=90 minutes		Up to 6 months
Evaluate withdrawal relief at t=5 through t=90 minutes	We measure withdrawal relief using the Minnesota Withdrawal Scale (MNWS). We administer this questionnaire at each timepoint along the standardized scale of t=0, t=5, t=15, t=30, t=60 and t=90. The MNWS includes a minimum value of "none" and a maximum value or "severe." The higher scores indicate increased withdrawal symptoms and lower scores indicate lessened or no withdrawal symptoms.	Up to 6 months
Evaluate product appeal across all 3 products	Product appeal will be assessed using several scales, including the Modified E-Cigarette Smoking Questionnaire (mCEQ), the Product Evaluation Scale (PES), the Adapted Drug Effects Liking Scale, and the Study Product Effects Liking Scale which are administered after the final timepoint of each study visit. For both the mCEQ and PES, the minimum scale value is "not at all" and the maximum scale value is "extremely." Higher scores can mean both better or worse depending on the question. Ex: "Was using your smokeless tobacco satisfying?" and "Did using your smokeless tobacco make you nauseous?" are both questions on each scale, so a higher score would vary in meaning based on the question. For the Adapted Drug Effects Liking and Study Product Effects Liking scales, minimum values include "not at all" and maximum value includes "very pleasant." With the exception of one question on the Study Product Effects Liking Scale, a higher score indicates increased enjoyment of the product.	Up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1 and 2: Nicotine pharmacokinetics	Will use linear or logistic mixed effects regression models (with a random subject effect) to assess the main effects of product on plasma nicotine delivery.	Up to 6 months
Subjective effects - likability and substitutability of product compared to cigarette smoking will be assessed	Will use linear or logistic mixed effects regression models (with a random subject effect) to assess the main effects of product on subjective effects.	Up to 6 months
Aim 1: Intentions to use and switch to NPs - quit intentions will be assessed using a 10 question survey	Will use linear or logistic mixed effects regression models (with a random subject effect) to assess the main effects of product behavioral intentions.	Up to 6 months
Aim 2: Public health effect of NPs in adult smokers - if NPs can be used as a substitute for cigarette smoking.	Public health impact of NPs in adult smokers as an alternative for cigarette smoking.	Up to 6 months

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Brittney L Keller-Hamilton, PhD, MPH, Ohio State University Comprehensive Cancer Center

Publications and helpful links

General Publications

• Keller-Hamilton B, Alalwan MA, Curran H, Hinton A, Long L, Chrzan K, Wagener TL, Atkinson L, Suraapaneni S, Mays D. 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. Addiction. 2024 Mar;119(3):464-475. doi: 10.1111/add.16355. Epub 2023 Nov 14.
• Keller-Hamilton B, Curran H, Alalwan M, Hinton A, Brinkman MC, El-Hellani A, Wagener TL, Chrzan K, Atkinson L, Suraapaneni S, Mays D. Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial. Nicotine Tob Res. 2024 May 7:ntae079. doi: 10.1093/ntr/ntae079. Online ahead of print.

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): April 18, 2023

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: OSU-21257; NCI-2021-14062 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No