Metabolism of NNK in Japanese Americans

NCT ID: NCT04228952

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 16 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2025-04-14

Brief 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.

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.

Conditions

Smoking

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK

Intervention Type: COMBINATION_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.

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)

Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK

Intervention Type: COMBINATION_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.

Interventions

Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK

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.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. Japanese American - one, but preferably 2 biological parents of Japanese descent

2. 21 years or older

3. Daily smoker

4. 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.

5. Stable and good physical and mental health

6. Provided written informed consent to participate in the study

Exclusion Criteria

1. 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

2. Currently taking any medications that affect relevant metabolic enzymes

3. Experiencing medical conditions that might affect biomarkers of exposure and effect

4. Pregnant or nursing or planning on becoming pregnant during the study

5. Unable to read and understand English

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Hawaii

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dorothy K Hatsukami, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

P01CA138338

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2019NTUC208

Identifier Type: -

Identifier Source: org_study_id