Naproxen Pharmacogenetic Study (Project 1, Aim 2)
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|ClinicalTrials.gov Identifier: NCT04449471|
Recruitment Status : Recruiting
First Posted : June 26, 2020
Last Update Posted : June 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pharmacogenetics||Drug: Naproxen tablet||Phase 4|
This pharmacogenetics study will test the hypothesis that inheritance of a M1L variant in the CYP2C9 gene, which was first discovered in Yup'ik Alaska Native people, causes complete loss of function in CYP-2C9-dependent catalytic activity.
Study participants will be selected from a cross-sectional population of >750 Yup'ik men and women, ≥18 years, for whom CYP2C9 genotype has already been determined as part of a SNP discovery study, and who consented to be contacted for future research. There will be 15 participants in each of two genotyped groups ((1) Met1/Met1 and (2) Met1/Leu1 or Leu1/Leu1), for a total of 30 participants. The two groups will be matched for sex of the participants; the proportion determined by the composition of the least frequent Leu1 carrier group. The investigators will attempt to recruit a similar range of ages in each genotyped group and the widest range possible. Recruitment will occur in one of 10 communities in the Yukon-Kuskokwim delta that participated in our original SNP discovery study.
Participants will be asked to fast overnight prior to the study and will be allowed to eat ad libitum 2 hours after naproxen is taken. A fasting 13 ml venous blood sample will be collected from each participant for isolation of DNA and plasma. Spot urine will be collected from each participant as an analytic control the morning of the blood draw. At approximately 9 am, each participant will be given a single 220-mg dose of Naproxen, by mouth, with a glass of water. The total urine output over the next 24-hour will be collected by the participant and returned to the clinic the next day. The urine volume will be measured and recorded and two 5 mL aliquots will be frozen at -80°C and stored for unchanged drug and metabolite analysis analyses.
Total (conjugated and unconjugated) 6-O-Desmethyl naproxen and unchanged naproxen concentrations in urine will be measured by LC-MS/MS. A ratio of the total 6-O-desmethyl naproxen/naproxen (M/P) excreted in urine over 24-hours will be computed. 6-O-desmethyl naproxen is formed selectively by CYP2C9.
Pairwise comparison of the mean M/P ratios, assuming unequal variance, will be evaluated using a t-test to determine if there are significant differences in activity for carriers of the Leu 1 variant. The sample size provides 80% power to detect a difference, at a significance level of 0.05.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Healthy adults with predetermined CYP2C9 genotype will receive the probe drug, naproxen.|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Project 1: Program on Genetic and Dietary Predictors of Drug Response in Rural and AI/AN Populations (Naproxen Study)|
|Actual Study Start Date :||January 12, 2016|
|Estimated Primary Completion Date :||July 31, 2021|
|Estimated Study Completion Date :||July 31, 2022|
Experimental: Naproxen Tablet
Subjects will received a single 220-mg dose of naproxen sodium (Aleve) by mouth.
Drug: Naproxen tablet
For this single intervention arm, each subject will receive a single 220-mg dose of naproxen sodium (Aleve), followed by urine collection for 24-hours.
Other Name: Aleve
- 6-O-desmethyl naproxen/naproxen ratio [ Time Frame: 24-hours ]A ratio of the total mount of 6-O-desmethyl naproxen/unchanged naproxen in 24-hour urine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04449471
|Contact: Kenneth E. Thummel, PhDfirstname.lastname@example.org|
|Principal Investigator:||Kenneth E. Thummel, PhD||University of Washington|