PharmacogeneticsPhase 4NCT04449471
Naproxen Pharmacogenetic Study (Project 1, Aim 2)
A Phase 4 study testing Naproxen tablet in people with Pharmacogenetics, run by University of Washington at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pharmacogenetics
- What is being tested?
- Naproxen tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2016to 31 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239-3098
Bert B. Boyer, PhD, 503-494-3368, boyerbe@ohsu.edu
Scarlett Hopkins, RN, MA, 503-494-3369, hopkisca@ohsu.edu
About this study
Official title: Project 1: Program on Genetic and Dietary Predictors of Drug Response in Rural and AI/AN Populations (Naproxen Study)
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.
Read the detailed 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 -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.
- Conditions
- Pharmacogenetics
- Being tested
- Naproxen tablet
- Keywords
- CYP2C9, naproxen, polymorphism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naproxen tabletDrug
Also called Aleve
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.
| Study group | Role | What they receive |
|---|---|---|
| Naproxen Tablet | Experimental | Subjects will received a single 220-mg dose of naproxen sodium (Aleve) by mouth. Receives: Drug: Naproxen tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-O-desmethyl naproxen/naproxen ratio
A ratio of the total mount of 6-O-desmethyl naproxen/unchanged naproxen in 24-hour urine
Measured: 24-hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2020
- Study start12 Jan 2016
- Primary completion31 Jul 2021 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacogeneticsStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Healthy adults with predetermined CYP2C9 genotype will receive the probe drug, naproxen.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Oregon Health and Science University, National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Kenneth Thummel, University of Washington
- Investigators
- Kenneth E. Thummel, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04449471
- Sponsor's protocol ID
- SITE00000671
- Other IDs
- 5P01GM116691
- Status last verified
- Jun 2020
- First submitted
- 23 Jun 2020
- Last updated
- 29 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Project 1: Program on Genetic and Dietary Predictors of Drug Response in Rural and AI/AN Populations (Naproxen Study)
- ClinicalTrials.gov ID
- NCT04449471
- Acronym / sponsor ID
- SITE00000671
- Conditions
- Pharmacogenetics
- Keywords
- CYP2C9, naproxen, polymorphism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Oregon Health and Science University, National Institute of General Medical Sciences (NIGMS)
- Study start
- 12 Jan 2016 (actual)
- Primary completion
- 31 Jul 2021 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 26 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 -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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Healthy adults with predetermined CYP2C9 genotype will receive the probe drug, naproxen.
| Arm | Type | Receives |
|---|---|---|
| Naproxen Tablet | Experimental | Drug: Naproxen tabletSubjects will received a single 220-mg dose of naproxen sodium (Aleve) by mouth. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naproxen tabletAlso: AleveFor this single intervention arm, each subject will receive a single 220-mg dose of naproxen sodium (Aleve), followed by urine collection for 24-hours. | Drug | Naproxen Tablet |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth E. Thummel, PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naproxen tablet in people with Pharmacogenetics, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kenneth E. Thummel, PhD (205-543-0819, thummel@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-O-desmethyl naproxen/naproxen ratio (time frame: 24-hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2020.