Purine Metabolism Enzyme SNP to Uric Acid Production

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Keesler Air Force Base Medical Center
Sponsor:
Collaborator:
United States Air Force
Information provided by (Responsible Party):
Keesler Air Force Base Medical Center
ClinicalTrials.gov Identifier:
NCT01830725
First received: April 5, 2013
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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.


Condition
Gout
Hyperuricemia

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Relationship of Purine Metabolism Enzyme Single-Nucleotide Polymorphisms to Uric Acid Production and Response to Xanthine Oxidase Inhibitors

Resource links provided by NLM:


Further study details as provided by Keesler Air Force Base Medical Center:

Primary Outcome Measures:
  • Relationship of SNPs to gout, hyperuricemia, and dose of xanthine oxidase inhibitor needed to reach goal serum uric acid level of < 6 mg/dL. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    This study will test the relationship of 2107A>G XO to the dose of allopurinol needed to achieve a treatment goal of less than 6 mg/dL. It will also test whether or not SNPs affecting the gene for hypoxanthine phosphoribosyltransferase 1 (HPRT1) are related to gout, hyperuricemia, or the dose of XO inhibitor needed to reach a goal of 6 mg/dL. Relationships will be determined using typical non-parametric or parametric tests depending on the skew and skedasticity.

    - Determine the relationship of several SNPs in genes encoding HPRT1 and one XO SNP (2107A>G) to the dose of xanthine oxidase inhibitor needed to achieve a goal treatment uric acid level of less than 6 mg/dL.



Secondary Outcome Measures:
  • Determine frequency of SNPs tested [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (1) Measure minor allele frequency of all SNPs tested as the number of heterozygotes present in the population recruited divided by the total number of patients recruited.


Other Outcome Measures:
  • Determine relationship of XO SNP 2107A>G and several HPRT1 SNPs to hyperuricemia/gout. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    This study will test the relationship of 2107A>G XO to the dose of allopurinol needed to achieve a treatment goal of less than 6 mg/dL. It will also test whether or not SNPs affecting the gene for hypoxanthine phosphoribosyltransferase 1 (HPRT1) are related to gout, hyperuricemia, or the dose of XO inhibitor needed to reach a goal of 6 mg/dL. Relationships will be determined using typical non-parametric or parametric tests depending on the skew and skedasticity.

    - Determine relationship of XO SNP 2107A>G and several HPRT1 SNPs to hyperuricemia/gout.



Biospecimen Retention:   Samples With DNA

DNA will be banked for future studies as allowed by patient consent


Estimated Enrollment: 500
Study Start Date: December 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Gout/Hyperuricemia
Subjects with a diagnosis of hyperuricemia (defined as a uric acid of > 7.2 mg/dl) and/or gout.
Control
Approximate age and gender matched controls without hyperuricemia or gout

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01830725

Contacts
Contact: Matthew B Carroll, MD 2283763629 matthew.carroll.1@us.af.mil

Locations
United States, Mississippi
Keesler Medical Center Recruiting
Keesler AFB, Mississippi, United States, 39564
Contact: Matthew B Carroll, MD    228-376-3629    matthew.carroll.1@us.af.mil   
Principal Investigator: Matthew B Carroll, MD         
Sub-Investigator: Derek Smith, MD         
Sub-Investigator: Rishawn Carriere         
Sub-Investigator: Audrey D Greenwell         
Sponsors and Collaborators
Keesler Air Force Base Medical Center
United States Air Force
Investigators
Principal Investigator: Matthew B Carroll, MD Keesler Medical Center
  More Information

No publications provided

Responsible Party: Keesler Air Force Base Medical Center
ClinicalTrials.gov Identifier: NCT01830725     History of Changes
Other Study ID Numbers: FKE20120020H
Study First Received: April 5, 2013
Last Updated: April 9, 2013
Health Authority: United States: Federal Government

Keywords provided by Keesler Air Force Base Medical Center:
Xanthine Oxidase
Gout
Hyperuricemia
SNP
Single Nucleotide Polymorphisms

Additional relevant MeSH terms:
Hyperuricemia
Pathologic Processes
Uric Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014