Genetics of Hyperuricemia Therapy in Hmong

Completed

• Conditions: Hyperuricemia, Gout
• Interventions: Drug: Allopurinol

• Registration Number: NCT02371421
• Lead Sponsor: University of Minnesota

Brief Summary

To pursue this objective, we will be measuring uric acid at baseline and post 14 days of twice daily allopurinol therapy in 30 Hmong participants with documented gout or hyperuricemia and known genotype for key renal transporters of uric acid.

Detailed Description

Minnesota Hmong are a unique population of individuals of South East Asian descent who have been noted to have a higher prevalence of gout and gout related comorbidities compared to non-Hmong. Elevated levels of uric acid are thought to be at the root cause of gout. Elevated levels of serum uric acid can result from either overproduction and or under-excretion. Xanthine oxidase plays a key role in the breakdown of purines to form uric acid. Transporters in the kidney also play a key role in excretion and/or re-absorption of uric acid. The objective of this study is to explore whether genetic variations in renal transporters may influence the disposition of serum uric acid in response to a drug (allopurinol) as well as the disposition of its active metabolite (oxipurinol) which may also be a substrate for these same transporters responsible for uric acid disposition. Genetic variations unique to the Hmong population may explain their increased prevalence in gout and or perceived lack of responsiveness to the drug (allopurinol) used to treat the condition.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2015-02-19
• Study First Submitted QC: 2015-02-24
• Study First Posted: 2015-02-25
• Primary Completion: 2015-12
• Study Completion: 2016-12
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-11
• Last Update Posted: 2019-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Both parents are Hmong (self report)
• Self report history of gout, or
• History (within one year) of active use of xanthine oxidase inhibitors, or
• Evidence of serum uric acid ≥ 6mg/dL , or
• Serum uric acid < 6mg/dL with history of ≥ 2 gout episodes within the last 6 months
• Ability to provide informed consent for participation in the study
• Demonstrate understanding of the study procedures and ability to comply with the study drug for the entire length of the study
• Ability to obtain permission from treating clinician to allow stopping the drug for 10 days

Exclusion Criteria

• Pregnant women or women of childbearing age sexually active and not using any contraception
• estimated creatinine clearance (eCrCl) <30ml/min
• Elevated liver enzymes (3 x upper normal limit of liver function tests (AST and ALT))
• Contraindication to receiving allopurinol
• Active participation in other clinical trial (or within 30 days)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Allopurinol	Allopurinol	Participants with history of gout indicated by the use of allopurinol or participants who have high serum uric acid without contraindication to use allopurinol.

Primary Outcome Measures

Name	Time	Method
Steady state oxipurniol area under the serum concentration-time curve (AUC)	14 days	Differences in mean AUC across genotype groups
Percent change from baseline in serum uric acid	14 days

Secondary Outcome Measures

Name	Time	Method
Percent change from baseline in Uric Acid Fractional Excretion	14 days
Percent change from baseline in Uric Acid Renal Clearance	14 days

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States