Evaluation of Low and High Nicotine Tobacco Free Nicotine Pouches (Pack2Pouch)

Evaluation of Low and High Nicotine Tobacco Free Nicotine Pouches as a Harm Reducing Substitute for Combustible Cigarettes - (Pack2Pouch)

Tobacco-free oral nicotine pouches (such as Zyn brand) are a less harmful alternative to cigarette smoking. Pouches, however, contain nicotine, and addictive substance that is not risk-free. The present study is evaluating how well nicotine pouches, at different nicotine levels, help people switch away from smoking cigarettes. People who smoke cigarettes will be asked to answer questions about their tobacco product use and provide breath samples and cheek swab samples at an in-person visit to MUSC Charleston. Participants will then be provided with a 28-day supply of nicotine pouches, and will be asked to switch from smoking to pouches over the course of 4 weeks. Finally, participants will complete a final visit at MUSC, and will answer more questions about their tobacco use 1-month later.

Study Overview

• Status: Recruiting
• Conditions: Smoking Cessation; Nicotine Dependence; Cigarette Smoking
• Intervention / Treatment: Behavioral: High Nicotine Dose; Behavioral: Low Nicotine Dose

Detailed Description

The proposed research project evaluates the potential for tobacco-free oral nicotine pouches (TFNPs) to serve as harm reduction tools at two nicotine concentrations, inclusive of behavioral and biomarker outcomes, using a clinical trial design. Specifically, in a randomized pilot study, participants who smoke will be recruited and sent TFNPs to sample for 4 weeks in either high (6 mg) or low (3 mg) nicotine content strengths. Participants will report tobacco use behaviors and submit biological samples throughout the study. This design allows for evaluation of the effect of nicotine content within alternative, harm-reducing tobacco products on key outcomes including: 1) complete switching from cigarette smoking to non-cigarette product use; 2) cigarette smoking reduction; 3) changes in biomarkers of harm (DNA damage, respiratory symptoms), 4) nicotine dependence, and 5) subjective effects of product use.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Talia Ogretman; Phone Number: 843-259-8111; Email: ogretmet@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 21+
• current cigarette smoking (25+ days per previous month, 5 or more cigarettes/day, for greater than 1yr, greater than 100 lifetime cigarettes)
• have not used TNFPs more than 5 times during their lifetime
• willing and able to attend 2 in-person visits in Charleston (to assess biomarkers)
• have internet access

Exclusion Criteria:

• Lack of proficiency in English.
• Use of other combustible tobacco products (i.e., cigars, cigarillos, hookahs) and/or other non-combusted nicotine/tobacco products (i.e., e-cigarettes, smokeless tobacco) in the past 30 days.
• Current use of smoking cessation medications (i.e., varenicline, bupropion, nicotine replacement therapy).
• Use of marijuana within the past month, and unwillingness to abstain from marijuana during course of study.
• Medical conditions contraindicated to NRT use (including pregnancy, breastfeeding, and nursing, past month myocardial infarction, current untreated cardiac arrhythmia, current severe angina, current uncontrolled severe vascular disease).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Nicotine; High dosage nicotine pouches (6mg)	Behavioral: High Nicotine Dose; Will receive a 5-week supply of 6 mg Zyn pouches. Those who smoke 5-20 cigarettes per day will receive 1 tin per day = 35 tins, whereas those who smoke more will receive 2 tins/day [70 tins])
Experimental: Low Nicotine; Low dosage nicotine pouches (3mg)	Behavioral: Low Nicotine Dose; Will receive a 5-week supply of 3 mg Zyn pouches. Those who smoke 5-20 cigarettes per day will receive 1 tin per day = 35 tins, whereas those who smoke more will receive 2 tins/day [70 tins])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Switching	Switching will be defined at 7-day point-prevalence biochemically-confirmed abstinence from cigarettes alongside self-reported use of nicotine pouches. Non-responders and missing data will be coded as smoking.	Day 28 and Day 56
Smoking Reduction	Baseline and daily survey data will be used to calculate the change of smoking (average cigarettes per day) between groups from baseline to end of sampling.	Day 28 and Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tobacco-Free Oral Nicotine Pouches (TFNP) Use	Daily surveys will capture number of days of TFNP use, regardless of smoking.	Day 28

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Amanda Palmer, PhD., Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 28, 2027

Study Registration Dates

• First Submitted: November 1, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Actual): November 7, 2024

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Smoking
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Health Behavior; Tobacco Smoking; Tobacco Use; Tobacco Use Disorder; Smoking; Smoking Cessation; Cigarette Smoking; 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: Pro00139710; 5K12DA031794 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified self-report data and outcomes from biosample analyses will be shared upon reasonable request. Biological samples will not be shared.
• IPD Sharing Time Frame: Data and supporting information will be shared 1 year after study results are published.
• IPD Sharing Access Criteria: Academic researchers who are not affiliated with or funded by the tobacco industry (including their consultants and non-profit organizations) may request access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

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