Metabolism of NNK in Japanese Americans

University of Minnesota (UMN)

Status: Completed

Conditions: Smoking

Treatments: Combination Product: Modified Natural American Spirit-Tan or Green cigarettes injected with labeled NNK

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04228952

P01CA138338 (U.S. NIH Grant/Contract)

2019NTUC208

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

16 participants in 2 patient groups

Smokers with very low or no CYP2A6 activity

Description:

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).

Treatment:

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

Smokers with high CYP2A6 activity

Description:

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)

Treatment:

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