Clinical trial NCT01830725: Purine Metabolism Enzyme SNP to Uric Acid Production
Official title: Relationship of Purine Metabolism Enzyme Single-Nucleotide Polymorphisms to Uric Acid Production and Response to Xanthine Oxidase Inhibitors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gout
Hyperuricemia
Keywords: Xanthine Oxidase
Gout
Hyperuricemia
SNP
Single Nucleotide Polymorphisms
Lead sponsor: Keesler Air Force Base Medical Center
Sponsor class: FED
Collaborators: name: United States Air Force
First posted: 2013-04-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients for either the gout/hyperuricemia group or the control group will be recruited at the time of their evaluation in either the Internal Medicine (IM) Clinic or IM Specialties Clinic.

Brief summary: Determine whether a relationship exists between polymorphisms of the genes XDH, HPRT1, and PRPS1 and gout, hyperuricemia, or the dose of xanthine oxidase (XO) inhibitors to reach a goal serum uric acid of less than 6 mg/dL. This study is observational in nature as no dose adjustment of XO inhibitors will be made by study investigators.

Detailed description: Background: Our recent gout study demonstrated a relationship between the xanthine oxidase (XO) single nucleotide polymorphism (SNP) 2107A\>G to the dose of allopurinol needed to reach a goal serum uric acid level of 6 mg/dL or less. This study had some limitations but suggests that specific SNPs could be related to dose of allopurinol needed to treat.

Objective: To determine the relationship of multiple purine enzyme SNPs of genes encoding PRPS1, HPRT1, and XO to the dose of xanthine oxidase inhibitor needed to achieve a goal treatment uric acid level of less than 6 mg/dL. Another primary outcome will be to determine relationship of two XO SNPs to hyperuricemia/gout. A secondary outcome will be to determine the frequency of these SNPs tested.

Design: Patients will be consented for enrollment in either the gout/hyperuricemia group or a control group. Control group patients will have neither gout nor hyperuricemia. No patients will be enrolled if they are overproducers of uric acid. It is anticipated that 200 patients will be enrolled in each group for a total of 400 patients over the next 2 years.

Eligibility criteria: Inclusion Criteria:

* The study will be open to all adults over age 18 years of age who satisfy at least one of the conditions below:
* Have asymptomatic hyperuricemia (serum uric acid level \> 7.0 mg/dL) on at least 2 separate occasions,
* Clinical diagnosis of gout,
* Have neither asymptomatic hyperuricemia or gout but will serve as part of the control group (approximate age/gender matched control)

Exclusion Criteria:

* To best isolate the relationship between purine enzyme SNPs to hyperuricemia or gout and its treatment, factors which could elevate the serum uric acid level independent of protein function need to be excluded. Specifically, patients who are "overproducers" of serum uric acid will be excluded:
* Have a myeloproliferative disorder (hematologic malignancy such as leukemia or lymphoma)
* Are actively receiving therapy for any neoplasia (aside from non-melanoma skin cacner)
* Have greater than 5% of skin involvement from psoriasis
* Have a known history of xanthinuria
* Consume more than 14 drinks per week of alcoholic beverages

Patients that are pregnant or nursing will not be enrolled. Patients to be enrolled in the control group will also be excluded from enrollment if they have any of the conditions above.

Primary outcomes:
measure: Relationship of SNPs to gout, hyperuricemia, and dose of xanthine oxidase inhibitor needed to reach goal serum uric acid level of < 6 mg/dL.
timeFrame: 2 years
Secondary outcomes:
measure: Determine frequency of SNPs tested
timeFrame: 2 years
Other outcomes:
measure: Determine relationship of XO SNP 2107A>G and several HPRT1 SNPs to hyperuricemia/gout.
timeFrame: 2 years
Locations:
city: Keesler AFB
country: United States
facility: Keesler Medical Center
state: Mississippi
Study officials:
affiliation: Keesler Medical Center
name: Matthew B Carroll, MD
role: PRINCIPAL_INVESTIGATOR
References: