Metabolism of NNK in Japanese Americans

يمكن للمستخدمين المسجلين فقط ترجمة المقالات

الدخول التسجيل فى الموقع

يتم حفظ الارتباط في الحافظة

الحالةلم يتم التجنيد بعد

الرعاة

Masonic Cancer Center, University of Minnesota

المتعاونون

University of Hawaii

تجربة سريرية: NCT04228952

BioSeek: nct04228952

الكلمات الدالة

نبذة مختصرة

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.

وصف

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.

تواريخ

آخر التحقق:	04/30/2020
تم الإرسال لأول مرة:	01/08/2020
تم إرسال التسجيل المقدر:	01/12/2020
أول نشر:	01/13/2020
تم إرسال آخر تحديث:	05/03/2020
آخر تحديث تم نشره:	05/05/2020
تاريخ بدء الدراسة الفعلي:	10/31/2020
تاريخ الإنجاز الأساسي المقدر:	05/31/2021
التاريخ المتوقع لانتهاء الدراسة:	05/31/2024

حالة أو مرض

Smoking

التدخل / العلاج

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

مرحلة

مجموعات الذراع

ذراع	التدخل / العلاج
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).
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)

معايير الأهلية

الأعمار المؤهلة للدراسة	21 Years إلى 21 Years
الأجناس المؤهلة للدراسة	All
طريقة أخذ العينات	Non-Probability Sample
يقبل المتطوعين الأصحاء	نعم
المعايير	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

النتيجة

مقاييس النتائج الأولية

1. Correlation of CYP2A6 genotype on the level of NNK α-hydroxylation administered [pyridine-D4]-D4 NNK. [7 days]

Comparison between the means of the two groups (null versus average CYP2A6) in smokers receiving [Pyridine D4]-NNK. The extent of NNK α-hydroxylation in the two groups will be described by a ratio of NNK metabolites, D4- α-hydroxymethyl NNK Gluc (or other products of α-hydroxylation) to D4-NNAL. The ratio is used as a measure of the pathway as a percent of dose.

2. NNK metabolic profiles [7 days]

Characterization of metabolites variation and covariation of NNK, NNAL-N-oxide, NNAL-glucuronides, α-hydroxy glucuronides and other NNK metabolites identified in smokers receiving [Pyridine D4]-NNK

Metabolism of NNK in Japanese Americans

الكلمات الدالة

نيكوتين

بيريدين

سرطان الرئة

نمو الورم

سرطان

butanone