Metabolism of NNK in Japanese Americans

NCT04228952 | Completed Results DMC FDA Drug

• 2 other identifiers: 2019NTUC208P01CA138338
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Smoking

Keywords

CYP2A6, Nicotine Metabolite Ratio, NNAL, NNK α-hydroxylation

Outcome Measures

Primary Outcomes (1)

• 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)

  7 days

Study Arms (2)

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).

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)

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

Interventions

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.

Smokers with high CYP2A6 activity; Smokers with very low or no CYP2A6 activity

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Japanese American Smokers

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• University of Hawaii: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

24 hour urine and blood samples

MeSH Terms

Conditions

Smoking

Condition Hierarchy (Ancestors)

Behavior

Results Point of Contact

• Title: Susan Murphy, PhD
• Organization: Masonic Cancer Center

murph062@umn.edu

612-624-7633

Study Officials

• Dorothy K Hatsukami, Ph.D

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 14, 2020
• Study Start: September 1, 2020
• Primary Completion: October 15, 2021
• Study Completion: April 14, 2025
• Last Updated: August 1, 2025
• Results First Posted: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available after papers are accepted for publication
• Access Criteria: Data generated by this grant will be made to outside investigators, according to the Guidance at http://grants.nih.gov/grants/policy/data\ sharing/data\ sharing\ guidance.htm.

Locations

US (1)