Naproxen Pharmacogenetic Study (Project 1 Aim 2)

  • STATUS
    Recruiting
  • participants needed
    30
  • sponsor
    University of Washington
Send
Updated on 16 February 2024
See if I qualify

Summary

This is a mechanism-based study in healthy adults to determine the effect of the CYP2C9 M1L gene polymorphism on the functional activity of the encoded CYP2C9 enzyme towards the probe substrate naproxen. CYP2C9 activity will be evaluated by measurement of O-desmethyl naproxen and unchanged naproxen in 24-hour urine following administration of a single oral dose of naproxen (Aleve) in Yup'ik Alaska Native adult men and women who were previously determined in a separate observational study to be homozygous for the CYP2C9*1 allele or a carrier of the CYP2C9 M1L allele.

Description

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 -80C 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.

Details
Condition Pharmacogenetics
Age 18years - 100years
Treatment Naproxen tablet
Clinical Study IdentifierNCT04449471
SponsorUniversity of Washington
Last Modified on16 February 2024

Eligibility

 Yes No Not Sure

Inclusion Criteria

No history of significant medical conditions including cardiac, pulmonary, gastrointestinal, or renal disease, HIV, or history of asthma, urticaria, or allergic-type reactions with aspirin (ASA) or other NSAID (nonsteroidal anti-inflammatory drug)
Both males or females 18 years and older
Self-identified as Yup'ik or Cup'ik
Able to read and understand English or Yup'ik
Able to provide informed consent
Women not currently pregnant or lactating

Exclusion Criteria

Individuals with any significant chronic medical condition, including cardiac, pulmonary, hepatic, gastrointestinal, or renal disease, HIV, or history of asthma, urticaria, or allergic-type reactions with aspirin (ASA) or other NSAID
Individuals less than 18 years of age
Individuals unable to read and understand English or Yup'ik
Individuals unable to provide informed consent
Individuals taking drugs or natural products known to affect the metabolic activity of CYP2C9 (e.g., rifampin, carbamazepine, barbiturates, phenytoin, valproic acid, fluconazole, ketoconazole, miconazole, amiodarone, fluvastatin and milk thistle
Women who are pregnant or lactating
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
Message sent successfully.
We have submitted the information you provided to the research team at the location you chose. For your records, we have sent a copy of the message to your email address.
If you would like to be informed of other studies that may be of interest to you, you may sign up for Patient Notification Service.
Sign up

Send a message

Enter your contact details to connect with study team

Investigator Avatar

Primary Contact

First name*
Last name*
Email*
Phone number*
Other language

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer
Add a private note
  • abc Select a piece of text.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.