Smokeless TobaccoPhase 1NCT03998735
Nornicotine in Smokeless Tobacco as a Precursor for Carcinogen Exposure
A Phase 1 study testing Herbal Snuff (Smokeless Tobacco) in people with Smokeless Tobacco, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
Our goal in this study is to investigate the extent of endogenous nitrosation of nornicotine in smokeless tobacco users as a function of nornicotine content in smokeless products. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Smokeless Tobacco
- What is being tested?
- Herbal Snuff (Smokeless Tobacco)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2021to Aug 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female adult smokeless tobacco users 18-65 years of age, using at least 3 tins of product per week for 6 months;
- Used the same brand for >80% of their smokeless tobacco use over the course of at least 6 months, and used this brand exclusively for at least two weeks prior to the eligibility screening;
- Not smoking or using any other nicotine or tobacco product in the past 2 weeks (expired CO < 6 ppm);
- Participants are in good physical health (no unstable medical condition) and good general oral health as determined by the licensed medical professional;
- Participants are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse) as determined by the licensed medical professional;
- Participants who are not taking any medications that affect relevant metabolic enzymes;
- Women who are not pregnant or nursing or planning to become pregnant;
- Participants have provided written informed consent to participate in the study.
Who cannot join
- Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data as determined by the licensed medical professional;
- Vital signs out of range as determined by the licensed medical professional (participants failing for vital signs will be allowed to re-screen once):
- Evident poor oral health (significant gum recession, dental caries, tooth loss) as determined by the general oral health status check;
- Excessive drinking (e.g., 5 or more drinks daily) or problems with drinking or drugs (e.g., self-report of binge drinking alcohol or treatment for drug or alcohol abuse within last 3 months); to be assessed by PI or licensed medical professional;
- Regular smoking or tobacco use (e.g., greater than once a week) other than oral smokeless tobacco products;
- Currently (within the past 2 weeks) using nicotine replacement or other tobacco cessation products (to minimize confounding effects of another product);
Trial locations and contacts
1 site in 1 country.
About this study
Our goal in this study is to investigate the extent of endogenous nitrosation of nornicotine in smokeless tobacco users as a function of nornicotine content in smokeless products. This study will lead to an understanding of the endogenous formation of NNN from nornicotine in humans, and will also investigate the effect of the reduction of nornicotine content in smokeless tobacco on the extent of endogenous NNN formation. The knowledge gained in this study will lead to the development of recommendations for the regulation, or potentially elimination, of nornicotine in smokeless tobacco products in order to minimize exposure to NNN in the users of these products.
- Conditions
- Smokeless Tobacco
- Being tested
- Herbal Snuff (Smokeless Tobacco)
- Medical subject headings
- Tobacco Use
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Herbal Snuff (Smokeless Tobacco)Drug
4 levels of [D4]nornicotine in herbal snuff
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (N=15) | Experimental | 160 µg/g herbal snuff, median level found in commercial moist snuff Receives: Drug: Herbal Snuff (Smokeless Tobacco) |
| Group 2 (N=15) | Experimental | 70 µg/g herbal snuff, lowest level found in commercial moist snuff (rounded) Receives: Drug: Herbal Snuff (Smokeless Tobacco) |
| Group 3 (N=15) | Experimental | 3.5 µg/g herbal snuff, 5% of the lowest level found in commercial moist snuff Receives: Drug: Herbal Snuff (Smokeless Tobacco) |
| Group 4(N=10) | Active comparator | 0 µg/g herbal snuff, control group will use unmodified herbal snuff Receives: Drug: Herbal Snuff (Smokeless Tobacco) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate endogenous formation of NNN in smokeless tobacco users.
Presence of urinary [pyridine-D4]NNN ([D4]NNN)
Measured: 2 Weeks
To investigate endogenous formation of NNN in smokeless tobacco users.
Level of urinary [pyridine-D4]NNN ([D4]NNN) present
Measured: 2 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2019
- Study start19 Oct 2021
- Primary completion1 Aug 2025
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smokeless TobaccoStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Irina Stepanov, PhD, Principal investigator, University of Minnesota, Division of Environmental Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03998735
- Sponsor's protocol ID
- 2019NTLS123
- Other IDs
- SPH-2019-23251
- Status last verified
- Nov 2025
- First submitted
- 24 Jun 2019
- Last updated
- 26 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nornicotine in Smokeless Tobacco as a Precursor for Carcinogen Exposure
- ClinicalTrials.gov ID
- NCT03998735
- Acronym / sponsor ID
- 2019NTLS123
- Conditions
- Smokeless Tobacco
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 1 Aug 2025 (actual)
- Study completion
- Aug 2026 (estimated)
- First posted
- 26 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our goal in this study is to investigate the extent of endogenous nitrosation of nornicotine in smokeless tobacco users as a function of nornicotine content in smokeless products. This study will lead to an understanding of the endogenous formation of NNN from nornicotine in humans, and will also investigate the effect of the reduction of nornicotine content in smokeless tobacco on the extent of endogenous NNN formation. The knowledge gained in this study will lead to the development of recommendations for the regulation, or potentially elimination, of nornicotine in smokeless tobacco products in order to minimize exposure to NNN in the users of these products.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 (N=15) | Experimental | Drug: Herbal Snuff (Smokeless Tobacco)160 µg/g herbal snuff, median level found in commercial moist snuff |
| Group 2 (N=15) | Experimental | Drug: Herbal Snuff (Smokeless Tobacco)70 µg/g herbal snuff, lowest level found in commercial moist snuff (rounded) |
| Group 3 (N=15) | Experimental | Drug: Herbal Snuff (Smokeless Tobacco)3.5 µg/g herbal snuff, 5% of the lowest level found in commercial moist snuff |
| Group 4(N=10) | Active comparator | Drug: Herbal Snuff (Smokeless Tobacco)0 µg/g herbal snuff, control group will use unmodified herbal snuff |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female adult smokeless tobacco users 18-65 years of age, using at least 3 tins of product per week for 6 months;
- Used the same brand for >80% of their smokeless tobacco use over the course of at least 6 months, and used this brand exclusively for at least two weeks prior to the eligibility screening;
- Not smoking or using any other nicotine or tobacco product in the past 2 weeks (expired CO < 6 ppm);
- Participants are in good physical health (no unstable medical condition) and good general oral health as determined by the licensed medical professional;
- Participants are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse) as determined by the licensed medical professional;
Key exclusion criteria (6 listed)
- Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data as determined by the licensed medical professional;
- Vital signs out of range as determined by the licensed medical professional (participants failing for vital signs will be allowed to re-screen once):
- Evident poor oral health (significant gum recession, dental caries, tooth loss) as determined by the general oral health status check;
- Excessive drinking (e.g., 5 or more drinks daily) or problems with drinking or drugs (e.g., self-report of binge drinking alcohol or treatment for drug or alcohol abuse within last 3 months); to be assessed by PI or licensed medical professional;
- Regular smoking or tobacco use (e.g., greater than once a week) other than oral smokeless tobacco products;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Herbal Snuff (Smokeless Tobacco)4 levels of [D4]nornicotine in herbal snuff | Drug | Group 1 (N=15), Group 2 (N=15), Group 3 (N=15), Group 4(N=10) |
Primary outcome
To investigate endogenous formation of NNN in smokeless tobacco users.
Time frame: 2 Weeks
Presence of urinary [pyridine-D4]NNN ([D4]NNN)
To investigate endogenous formation of NNN in smokeless tobacco users.
Time frame: 2 Weeks
Level of urinary [pyridine-D4]NNN ([D4]NNN) present
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Irina Stepanov, PhD principal investigator
University of Minnesota, Division of Environmental Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Herbal Snuff (Smokeless Tobacco) in people with Smokeless Tobacco, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To investigate endogenous formation of NNN in smokeless tobacco users. (time frame: 2 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.