Informing Oral Nicotine Pouch Regulations to Promote Public Health

March 12, 2024 updated by: Brittney Keller-Hamilton, Ohio State University Comprehensive Cancer Center
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Other: Text Message-Based Navigation Intervention
Receive text with a link to daily diary surveys
Other Names:
  • Automated Text Message-Based Navigation
  • Text Message-Based Navigation
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Other: Text Message-Based Navigation Intervention
Receive text with a link to daily diary surveys
Other Names:
  • Automated Text Message-Based Navigation
  • Text Message-Based Navigation
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Other: Text Message-Based Navigation Intervention
Receive text with a link to daily diary surveys
Other Names:
  • Automated Text Message-Based Navigation
  • Text Message-Based Navigation
Experimental: 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.
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample and oral mucosa sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cigarette
Smoke usual brand cigarette
Drug: Nicotine Oral Pouch
Insert low FBN R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert low FBN > 99% S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high R/S ONP
Other Names:
  • ZYN
Drug: Nicotine Oral Pouch
Insert high FBN > 99% ONP
Other Names:
  • ZYN
Drug: Smokeless Tobacco
Insert ST
Other Names:
  • Smoking, Tobacco and Cancer - Smokeless Tobacco
Other: Text Message-Based Navigation Intervention
Receive text with a link to daily diary surveys
Other Names:
  • Automated Text Message-Based Navigation
  • Text Message-Based Navigation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increased nicotine delivery
Time Frame: Up to 3 months
Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of oral nicotine pouches (ONPs) relative to cigarettes and smokeless tobacco (ST). Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.
Up to 3 months
Liking
Time Frame: Up to 3 months
Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of ONPs relative to cigarettes and ST. Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.
Up to 3 months
Craving/withdrawal suppression
Time Frame: Up to 3 months
Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of ONPs relative to cigarettes and ST. Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.
Up to 3 months
Rate of switching to ONP
Time Frame: Up to 3 months
Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of ONPs relative to cigarettes and ST. Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.
Up to 3 months
Rate of switching to ONPs
Time Frame: Up to 3 months
Data will be used to evaluate the effects of nicotine concentration, form and isomer on switching from cigarettes or ST to ONPs either partially or completely. Logistic regression models will be used to examine whether differences in form and isomer significantly impact switching.
Up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

February 14, 2024

First Submitted That Met QC Criteria

March 12, 2024

First Posted (Actual)

March 18, 2024

Study Record Updates

Last Update Posted (Actual)

March 18, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSU-23116
  • U54CA287392 (U.S. NIH Grant/Contract)
  • NCI-2024-00666 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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