Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • UT Southwestern-Other
  • UT Southwestern-Clinical Translational Research Center (CTRC)
  • UT Southwestern Ambulatory Services
  • Parkland Health & Hospital System

Ashlei Johnson-Wilder

Principal Investigator
Naim Maalouf, M.D.

Official Title

Effects of Pharmacological Reversal of Hyperuricemia on Features of the Metabolic Syndrome

Brief Overview

This study is being done to evaluate whether the medication, febuxostat, can improve the
degree of insulin resistance and other features of the metabolic syndrome (high blood
pressure, elevated insulin levels, excess body fat around the waist, and/or high
cholesterol) by lowering uric acid levels in the blood.


The metabolic syndrome (MS) is characterized by a constellation of metabolic features
including dyslipidemia, hyperglycemia, hypertension, obesity, and insulin resistance. This
cluster of features is strongly associated with type 2 diabetes, atherosclerotic
cardiovascular disease, and increased cardiovascular and all-cause mortality. Hyperuricemia
(elevated serum uric acid) is associated with insulin resistance and features of the MS in
cross-sectional epidemiological studies. However, it remains unclear whether this
association is causal or simply coincidental. If hyperuricemia CAUSES insulin resistance,
then lowering serum uric acid by pharmacological means may result in improved insulin
sensitivity and reversal of features of the metabolic syndrome. In some recent small
studies, lowering serum uric acid with allopurinol was associated with improvement in some
of the features and/or complications of the MS: Allopurinol use resulted in reduction in
blood pressure in adolescents and improvement in exercise capacity in patients with chronic
stable angina. A low urine pH is strongly associated with insulin resistance, and individual
features of the metabolic syndrome. Similarly, a low fractional excretion of uric acid is
also associated with metabolic syndrome feature. We therefore would like to examine the
effect on febuxostat on these two parameters which have been linked with the metabolic

The goal of this study is to evaluate whether pharmacological lowering of serum uric acid
with the medication febuxostat is associated with improvement in the degree of insulin
resistance and various features of the metabolic syndrome.

Participant Eligibility

Inclusion Criteria:

- Age > 21 years

- Gout

- Hyperuricemia (serum uric acid > 7.0 mg/dl in men and >6.0 mg/dl in women).

Exclusion Criteria:

- Current treatment with insulin, azathioprine, mercaptopurine, or theophylline.

- Treatment with febuxostat, allopurinol or other uricosuric agents (including
losartan, probenecid) within the past year

- Uncontrolled hypertension (clinic systolic blood pressure > 160 mmHg or diastolic
blood pressure > 90 mmHg within the past 6 months)

- Uncontrolled diabetes mellitus (HbA1c > 7%)

- estimated GFR < 60 ml/min by MDRD

- Elevated liver function tests (AST or ALT greater than 3 times the upper limit of

- Pregnancy