Metabolism of NNK in 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.

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Key information

Conditions

Smoking Behavior

Age range

21 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

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

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.

Primary outcomes

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)

Sponsors and collaborators

Lead sponsor

Masonic Cancer Center, University of Minnesota

Other

Collaborators

National Cancer Institute (NCI)
University of Hawaii

Registry information

Official study title

STUDY 2: CLINICAL PROTOCOL Metabolism of NNK Among Japanese Americans

Important dates

Study start: 2020
Primary completion: 2021
Study completion: 2025
First posted: Jan 14, 2020
Registry last updated: Aug 1, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed