Informing Oral Nicotine Pouch Regulations to Promote Public Health

NCT ID: NCT06315881

Last Updated: 2025-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-13

Study Completion Date

2028-08-31

Brief Summary

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This clinical trial evaluates the characteristics of oral nicotine pouches (ONPs) to determine if they are a comparable substitute to cigarette or smokeless tobacco (ST) products. ONPs contain nicotine but no tobacco and are used primarily by adult tobacco uses in the United States (US). ONPs are recognized by the Food and Drug Administration as having lower risk than combustible cigarettes and are approved as a modified risk tobacco product. While ONPs have lower toxic risk than other tobacco products, acute and longer term harm related to their use has not been studied. Information gathered from this study may identify product characteristics of ONPs that improve successful switching from high-risk cigarettes or ST to lower risk ONPs.

Detailed Description

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PRIMARY OBJECTIVES:

I. Assess the effects of nicotine concentration, form, and isomer on the satisfaction and appeal of ONPs relative to cigarettes and ST.

II. Evaluate the effects of nicotine concentration, form, and isomer on switching from cigarettes or ST to ONPs.

EXPLORATORY OBJECTIVE:

I. Examine changes in oral microbiome-host interactions associated with degree of switching from cigarettes/ST to ONPs.

OUTLINE:

PHASE I: Participants are randomized to use one of the 4 study ONP products or their usual product brand of ST or cigarette in either the low or high nicotine concentration arm.

ARM I: Participants insert low free-base nicotine (FBN) R/S ONP product over 30 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

ARM II: Participants insert low FBN \> 99% S ONP product over 30 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

ARM III: Participants insert high R/S ONP product over 30 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

ARM IV: Participants insert high FBN \> 99% S ONP product over 30 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

ARM V: Participants insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

PHASE II:

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week.

CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use.

PHASE II SWITCH: Participants are randomized to switch to 1 of 4 study ONP.

ARM I: Participants insert low FBN R/S ONP for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

ARM II: Participants insert to low FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

ARM III: Participants insert to high R/S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

ARM IV: Participants insert high FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Conditions

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Tobacco-Related Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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PHASE I ARM I (low FBN R/S ONP)

Participants insert low free-base nicotine (FBN) R/S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert low FBN R/S ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

PHASE I ARM II (low FBN > 99% S ONP)

Participants insert low FBN \> 99% S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert low FBN \> 99% S ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

PHASE I ARM III (high FBN R/S ONP)

Participants insert high R/S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert high R/S ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

PHASE I ARM IV (high FBN > 99% ONP)

Participants insert high FBN \> 99% S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert high FBN \> 99% ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

PHASE I ARM V (Usual brand ST or cigarette)

Participants insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

PHASE II ARM I (low FBN R/S ONP)

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week.

CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use.

Participants insert low FBN R/S ONP for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert low FBN R/S ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

Text Message-Based Navigation Intervention

Intervention Type OTHER

Receive text with a link to daily diary surveys

PHASE II ARM II (low FBN > 99% S ONP)

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week.

CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use.

Participants insert to low FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert low FBN \> 99% S ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

Text Message-Based Navigation Intervention

Intervention Type OTHER

Receive text with a link to daily diary surveys

PHASE II ARM III (high R/S ONP)

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week.

CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use.

Participants insert to high R/S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert high R/S ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

Text Message-Based Navigation Intervention

Intervention Type OTHER

Receive text with a link to daily diary surveys

PHASE II ARM IV (high FBN > 99% ONP)

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week.

CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use.

Participants insert high FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample and oral mucosa sample collection

Cigarette

Intervention Type DRUG

Smoke usual brand cigarette

Nicotine Oral Pouch

Intervention Type DRUG

Insert high FBN \> 99% ONP

Smokeless Tobacco

Intervention Type DRUG

Insert ST

Survey Administration

Intervention Type OTHER

Ancillary studies

Text Message-Based Navigation Intervention

Intervention Type OTHER

Receive text with a link to daily diary surveys

Interventions

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Biospecimen Collection

Undergo blood sample and oral mucosa sample collection

Intervention Type PROCEDURE

Cigarette

Smoke usual brand cigarette

Intervention Type DRUG

Nicotine Oral Pouch

Insert low FBN R/S ONP

Intervention Type DRUG

Nicotine Oral Pouch

Insert low FBN \> 99% S ONP

Intervention Type DRUG

Nicotine Oral Pouch

Insert high R/S ONP

Intervention Type DRUG

Nicotine Oral Pouch

Insert high FBN \> 99% ONP

Intervention Type DRUG

Smokeless Tobacco

Insert ST

Intervention Type DRUG

Survey Administration

Ancillary studies

Intervention Type OTHER

Text Message-Based Navigation Intervention

Receive text with a link to daily diary surveys

Intervention Type OTHER

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection ZYN ZYN ZYN ZYN Smoking, Tobacco and Cancer - Smokeless Tobacco Automated Text Message-Based Navigation Text Message-Based Navigation

Eligibility Criteria

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Inclusion Criteria

* Read and speak English
* At least 21 years old
* Willing to provide informed consent and abstain from all tobacco, nicotine, and marijuana use for at least 12 hours prior to Phase 1 study visits
* Willing to attend all study visits and use study ONPs
* Owns a smartphone and able to receive short messaging service (SMS) text messages with embedded survey link (for daily diary reports of ONP and other tobacco use)
* Negative pregnancy test produced during Phase 1 visits 1-5 and Phase 2 visit 1 if capable of becoming pregnant
* Exhaled carbon monoxide (CO) reading \< 10 (Phase 1)
* CIGARETTE SMOKERS ONLY: Established cigarette smoker (has smoked at least 100 cigarettes, has smoked daily for at least the past 3 months, now smokes at least 5 cigarettes per day)
* ST USERS ONLY: Established moist snuff user (has used moist snuff daily for at least the past 3 months, uses at least 1.5 cans/week (as in Pickworth et al., 2014)

Exclusion Criteria

* Unstable or significant psychiatric conditions (past and stable conditions will be allowed)
* History of cardiac event or distress within the past 3 months
* Currently pregnant, planning to become pregnant, or breastfeeding (will be verified with urine pregnancy test before each Phase 1 study visit \[acute use of usual product and study ONPs\] and Phase 2 study visit 1 \[distribution of study ONPs for outpatient ad libitum use\])
* Currently engaging in tobacco quit attempt, interested in quitting all tobacco, or planning on quitting all tobacco in the next 3 months
* Oral or systemic health issues that affect oral microbiome or epithelium, including having fewer than 21 teeth, diabetes mellitus, or autoimmune disease (e.g., rheumatoid arthritis, lupus)
* CIGARETTE SMOKERS ONLY: Use of non-cigarette tobacco products ≥ 10 of the past 30 days
* CIGARETTE SMOKERS ONLY: Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, or chronic obstructive pulmonary disease
* CIGARETTE SMOKERS ONLY: Roll-your-own cigarette smokers
* ST USERS ONLY: Use of non-moist-snuff tobacco products ≥ 10 of the past 30 days
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Brittney Keller-Hamilton

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Brittney L Keller-Hamilton, PhD, MPH

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

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Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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The Ohio State University Comprehensive Cancer Center

Role: CONTACT

800-293-5066

Facility Contacts

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Brittney L. Keller-Hamilton, PhD, MPH

Role: primary

614-366-9652

Related Links

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Other Identifiers

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NCI-2024-00666

Identifier Type: REGISTRY

Identifier Source: secondary_id

U54CA287392

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OSU-23116

Identifier Type: -

Identifier Source: org_study_id

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