Clinical trial NCT04228952: Metabolism of NNK in Japanese Americans
Official title: STUDY 2: CLINICAL PROTOCOL Metabolism of NNK Among Japanese Americans
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Smoking
Keywords: CYP2A6, Nicotine Metabolite Ratio, NNAL, NNK α-hydroxylation
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
Collaborators: name: University of Hawaii
name: National Cancer Institute (NCI)
First posted: 2020-01-14
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Japanese American Smokers

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.

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

Primary outcomes:
measure: Correlation of CYP2A6 genotype on the level of NNK α-hydroxylation administered [pyridine-D4]-D4 NNK.
timeFrame: 7 days
measure: NNK metabolic profiles
timeFrame: 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Dorothy K Hatsukami, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: