Genetics of Hyperuricemia Therapy in Hmong (GOUT-H)

Genomic Guided Assessment of Drug Therapy Effectiveness in Managing Hmong Adults With Hyperuricemia or Gout.

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.

Study Overview

• Status: Completed
• Conditions: Hyperuricemia, Gout
• Intervention / Treatment: Drug: Allopurinol

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 Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Hmong (self-report) adulst with gout as evidenced by use of uric acid-reducing medication.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Drug: Allopurinol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in Uric Acid Fractional Excretion	14 days
Percent change from baseline in Uric Acid Renal Clearance	14 days

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Robert J Straka, PharmD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: 1408M53223