Metabolism of NNK in Japanese Americans

Smoking Clinical Trial

Official title:

STUDY 2: CLINICAL PROTOCOL Metabolism of NNK Among Japanese Americans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04228952
• Other study ID #: 2019NTUC208
• Secondary ID: P01CA138338
• Status: Recruiting
• Start date: September 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Joni Jensen, MPH
• Phone: 612-624-5178
• Email: jense010[@]umn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2024
• Est. primary completion date: October 15, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Smoking

Intervention

Combination Product:
• 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.

Locations

Country	Name	City	State
United States	University of Hawaii Cancer Center	Honolulu	Hawaii

Sponsors (3)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota	National Cancer Institute (NCI), University of Hawaii

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of CYP2A6 genotype on the level of NNK a-hydroxylation administered [pyridine-D4]-D4 NNK.	Comparison between the means of the two groups (null versus average CYP2A6) in smokers receiving [Pyridine D4]-NNK. The extent of NNK a-hydroxylation in the two groups will be described by a ratio of NNK metabolites, D4- a-hydroxymethyl NNK Gluc (or other products of a-hydroxylation) to D4-NNAL. The ratio is used as a measure of the pathway as a percent of dose.	7 days
Primary	NNK metabolic profiles	Characterization of metabolites variation and covariation of NNK, NNAL-N-oxide, NNAL-glucuronides, a-hydroxy glucuronides and other NNK metabolites identified in smokers receiving [Pyridine D4]-NNK	7 days