Clinical trial NCT02371421: Genetics of Hyperuricemia Therapy in Hmong
Official title: Genomic Guided Assessment of Drug Therapy Effectiveness in Managing Hmong Adults With Hyperuricemia or Gout.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hyperuricemia, Gout
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2015-02-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hmong (self-report) adulst with gout as evidenced by use of uric acid-reducing medication.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percent change from baseline in serum uric acid
timeFrame: 14 days
measure: Steady state oxipurniol area under the serum concentration-time curve (AUC)
timeFrame: 14 days
Secondary outcomes:
measure: Percent change from baseline in Uric Acid Fractional Excretion
timeFrame: 14 days
measure: Percent change from baseline in Uric Acid Renal Clearance
timeFrame: 14 days
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Robert J Straka, PharmD
role: PRINCIPAL_INVESTIGATOR
References: