The Options 2 Study

A Randomized Comparative Effectiveness Trial of Nicotine Pouches for Cigarette Substitution: A Question of Public Health

The goal of this clinical trial is to investigate how well nicotine pouches and nicotine mini lozenges serve as substitutes for cigarettes when people try to switch from smoking to using these alternate nicotine products.

Participants will:

• Use nicotine pouches, nicotine mini lozenges, or no study product for a week and then try not to smoke for 3 weeks.
• Have 6 in-person research visits and 1 follow-up call
• Complete questionnaires at each study contact and use a smartphone app to record smoking and study product use

Study Overview

• Status: Recruiting
• Conditions: Smoking Cessation; Smoker
• Intervention / Treatment: Drug: Nicotine Pouches; Drug: Mini Nicotine lozenges

Detailed Description

Researchers currently lack critical data needed to appraise the potential for nicotine pouches to benefit public health. Specifically, they do not know how readily smokers will adopt pouches, how effectively they can substitute for cigarettes when smokers are trying to avoid smoking, the role of nicotine dose in the ability of pouches to serve as a substitute, or the mechanisms that facilitate or hinder successful product transition. This study will address these questions using a 4-arm randomized controlled trial of adults who smoke ≥5 cigarettes daily and are not planning to quit smoking in the next 30 days. This study will provide a rigorous evaluation of the potential efficacy of a relatively modified risk new nicotine product as a substitute for combusted cigarettes. The head-to-head comparison with FDA-approved mini lozenges can inform tobacco regulatory policy decisions.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mark Zehner; Phone Number: 608-262-7568; Email: mark.zehner@wisc.edu
• Study Contact Backup: Name: Megan Piper, PhD; Phone Number: 608-265-5472; Email: mep@ctri.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin
      • Contact: Megan Piper, PhD; Phone Number: 608-265-5472; Email: mep@ctri.wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 21 years old (i.e., able to legally purchase tobacco products)
• able to read and communicate in English
• no plans to quit smoking in the next 30 days
• willing to stop using nicotine replacement or varenicline
• willing to stop using bupropion (i.e., Wellbutrin, Zyban) if they are currently using it only for smoking cessation
• smoking ≥ 5 cigarettes per day for the past 6 months
• exhaled carbon monoxide ≥ 6 ppm
• no nicotine pouch or smokeless tobacco (including snus) use within the last 6 months

Exclusion Criteria:

• currently in treatment for psychosis or bipolar disorder
• currently taking bupropion for non-smoking cessation reasons (e.g., Wellbutrin for depression)
• currently pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3mg Nicotine Pouches; Participants will use 3mg nicotine pouches	Drug: Nicotine Pouches; 3mg or 6mg nicotine pouches; Other Names: ZYN
Experimental: 6mg Nicotine Pouches; Participants will use 6mg nicotine pouches	Drug: Nicotine Pouches; 3mg or 6mg nicotine pouches; Other Names: ZYN
Experimental: Nicotine Mini Lozenges; Participants will use mini lozenges with dosing based on time to first cigarette (2mg - 4mg)	Drug: Mini Nicotine lozenges; 2mg to 4mg mini lozenges
No Intervention: No Study Product; Participants randomized to this arm will use a mint candy during two different 30-minute laboratory sessions only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean number of cigarettes smoked per day during the 21-day switching period.	Participants will self-report on their cigarette use	Baseline to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cigarette craving	Participants will rate their craving for a cigarette using a 0-100 visual analog scale, where 0 = no craving and 100 = extreme craving after sampling their assigned study product after overnight abstinence from smoking	Baseline to 3 weeks
Mean units of study product used per day during the 7-days prior to the switching period	Participants will report their study product use via EMA	For 7-days leading up to the switching period
Mean units of study product used per day during the 21-day of the switching period	Participants will report their study product use via EMA	21-days of the switching period

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Megan Piper, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): July 30, 2029

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Health Behavior; Smoking Cessation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2024-1016; A534253 (Other Identifier: UW- Madison); 1R01CA291761-01 (U.S. NIH Grant/Contract); Protocol Version 8/22/25 (Other Identifier: UW Madison)

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
• product manufactured in and exported from the U.S.: No