SmokingNCT04228952
Metabolism of NNK in Japanese Americans
An observational study of Smoking, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The risk of lung cancer varies by individual and by ethnic/racial group. In this study the investigators will explore how individual differences in the metabolism of a tobacco-specific lung carcinogen may contribute to the variable risk of lung cancer between ethnic/racial groups. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Smoking
- What is being tested?
- Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2020to 14 Apr 2025
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Japanese American Smokers
Who may be able to join
- Japanese American - one, but preferably 2 biological parents of Japanese descent
- 21 years or older
- Daily smoker
- Eligible urinary ratios of total 3-hydroxycotinine to cotinine (3HC/COT):
- "Little or no-CYP2A6 activity" defined as a 3-hydroxycotinine:cotinine ratio of <0.6 or
- "Relatively high" CYP2A6 activity defined as a 3-hydroxycotinine:cotinine ratio of >3.0.
- Stable and good physical and mental health
- Provided written informed consent to participate in the study
Who cannot join
- Unwilling to avoid other nicotine containing products during the study and no use of any nicotine-containing products except cigarettes for 1 week prior to their study visits
- Currently taking any medications that affect relevant metabolic enzymes
- Experiencing medical conditions that might affect biomarkers of exposure and effect
- Pregnant or nursing or planning on becoming pregnant during the study
- Unable to read and understand English
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
About this study
Official title: STUDY 2: CLINICAL PROTOCOL Metabolism of NNK Among Japanese Americans
The risk of lung cancer varies by individual and by ethnic/racial group. In this study the investigators will explore how individual differences in the metabolism of a tobacco-specific lung carcinogen may contribute to the variable risk of lung cancer between ethnic/racial groups.
In this 10 day clinical trial, Japanese Americans will smoke a cigarette containing deuterium-labeled 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific lung carcinogen. The study cigarette will be smoked for 7 days.
This will allow for NNK metabolic profiling and determining the effect of CYP2A6 genotype on the level of NNK α-hydroxylation in Japanese Americans smokers using [pyridine- D4]-NNK containing cigarettes.
Read the detailed description
Eligible subjects will provide a baseline 24 hour urine sample. Study cigarettes spiked with labeled NNK will be provided to the subjects to smoke over a 7 day period. During this time, 24 hour urine samples will be collected over days 5, 6 and 7 on study cigarettes. Blood will be drawn on days 6 and 7 on study cigarettes. Samples will be analyzed for NNK metabolism.
- Conditions
- Smoking
- Being tested
- Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK
- Keywords
- CYP2A6, Nicotine Metabolite Ratio, NNAL, NNK α-hydroxylation
- Medical subject headings
- Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNKCombination product
American Spirit cigarettes will be modified by adding 0.300 μg [pyridine-D4]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco.
| Study group | Role | What they receive |
|---|---|---|
| Smokers with very low or no CYP2A6 activity | Japanese American smokers (daily > 5 cigarettes) with little or no CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of <0.6). Receives: Combination Product: Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK | |
| Smokers with high CYP2A6 activity | Japanese American smokers (daily > 5 cigarettes) with high CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of > 3.0) Receives: Combination Product: Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Ratio of D4-hydroxy Acid to D4- NNAL (an Estimate if NNK Alpha Hydroxylation)
Difference in means of the ratio of D4-hydroxy acid to D4- NNAL (an estimate if NNK alpha hydroxylation) for the two groups (null versus average CYP2A6 activity)
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start1 Sep 2020
- Primary completion15 Oct 2021
- Study completion14 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SmokingStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- University of Hawaii, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Dorothy K Hatsukami, Ph.D, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04228952
- Sponsor's protocol ID
- 2019NTUC208
- Other IDs
- P01CA138338
- Status last verified
- Jul 2025
- First submitted
- 9 Jan 2020
- Last updated
- 1 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available in two formats: Summary of the data (graphs and tables) and as raw individual-level data for analysis. Requests for data must be in writing, identify the affiliation and describe how the data will be used. Users agree not to transfer the data to other users and that the data are only to be used for research purposes. The PI will require requestors of data to sign a data and biospecimen sharing agreement that will ensure (1) Use of only for research purposes and not to identify any individual or personal information, (2) Data will be secure, (3) Destruction or return of data after data analysis and (4) Proper citation in publications or other written materials. A record of transfer of data and a copy of the dataset that was distributed will be kept by University of Minnesota.
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STUDY 2: CLINICAL PROTOCOL Metabolism of NNK Among Japanese Americans
- ClinicalTrials.gov ID
- NCT04228952
- Acronym / sponsor ID
- 2019NTUC208
- Conditions
- Smoking
- Keywords
- CYP2A6, Nicotine Metabolite Ratio, NNAL, NNK α-hydroxylation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- University of Hawaii, National Cancer Institute (NCI)
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 15 Oct 2021 (actual)
- Study completion
- 14 Apr 2025 (actual)
- First posted
- 14 Jan 2020 (actual)
- Results
- Posted 1 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The risk of lung cancer varies by individual and by ethnic/racial group. In this study the investigators will explore how individual differences in the metabolism of a tobacco-specific lung carcinogen may contribute to the variable risk of lung cancer between ethnic/racial groups.
In this 10 day clinical trial, Japanese Americans will smoke a cigarette containing deuterium-labeled 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific lung carcinogen. The study cigarette will be smoked for 7 days.
This will allow for NNK metabolic profiling and determining the effect of CYP2A6 genotype on the level of NNK α-hydroxylation in Japanese Americans smokers using [pyridine- D4]-NNK containing cigarettes.
Detailed description
Eligible subjects will provide a baseline 24 hour urine sample. Study cigarettes spiked with labeled NNK will be provided to the subjects to smoke over a 7 day period. During this time, 24 hour urine samples will be collected over days 5, 6 and 7 on study cigarettes. Blood will be drawn on days 6 and 7 on study cigarettes. Samples will be analyzed for NNK metabolism.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Smokers with very low or no CYP2A6 activity | – | Combination Product: Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNKJapanese American smokers (daily > 5 cigarettes) with little or no CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of <0.6). |
| Smokers with high CYP2A6 activity | – | Combination Product: Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNKJapanese American smokers (daily > 5 cigarettes) with high CYP2A6 activity (CYP2A6 activity defined as a ratio of trans-3-hydroxycotinine:cotinine ratio of > 3.0) |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Japanese American Smokers
Key inclusion criteria (8 listed)
- Japanese American - one, but preferably 2 biological parents of Japanese descent
- 21 years or older
- Daily smoker
- Eligible urinary ratios of total 3-hydroxycotinine to cotinine (3HC/COT):
- Stable and good physical and mental health
Key exclusion criteria (5 listed)
- Unwilling to avoid other nicotine containing products during the study and no use of any nicotine-containing products except cigarettes for 1 week prior to their study visits
- Currently taking any medications that affect relevant metabolic enzymes
- Experiencing medical conditions that might affect biomarkers of exposure and effect
- Pregnant or nursing or planning on becoming pregnant during the study
- Unable to read and understand English
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 |
|---|---|---|
| Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNKAmerican Spirit cigarettes will be modified by adding 0.300 μg [pyridine-D4]NNK to each cigarette so that the amount of total (deuterated plus unlabeled) NNK in these cigarettes is below 0.700 μg/g tobacco. | Combination product | Smokers with high CYP2A6 activity, Smokers with very low or no CYP2A6 activity |
Primary outcome
The Ratio of D4-hydroxy Acid to D4- NNAL (an Estimate if NNK Alpha Hydroxylation)
Time frame: 7 days
Difference in means of the ratio of D4-hydroxy acid to D4- NNAL (an estimate if NNK alpha hydroxylation) for the two groups (null versus average CYP2A6 activity)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Data will be available in two formats: Summary of the data (graphs and tables) and as raw individual-level data for analysis. Requests for data must be in writing, identify the affiliation and describe how the data will be used. Users agree not to transfer the data to other users and that the data are only to be used for research purposes. The PI will require requestors of data to sign a data and biospecimen sharing agreement that will ensure (1) Use of only for research purposes and not to identify any individual or personal information, (2) Data will be secure, (3) Destruction or return of data after data analysis and (4) Proper citation in publications or other written materials. A record of transfer of data and a copy of the dataset that was distributed will be kept by University of Minnesota.
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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.
Dorothy K Hatsukami, Ph.D principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Smoking, 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 5 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: finished, as of the sponsor's last update on 1 Aug 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Ratio of D4-hydroxy Acid to D4- NNAL (an Estimate if NNK Alpha Hydroxylation) (time frame: 7 days). 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 1 Aug 2025.