Clinical trial NCT01654276: Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome
Official title: Effects of Pharmacological Reversal of Hyperuricemia on Features of the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gout
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2012-07-31
Enrollment: 24
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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 syndrome.

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.

Eligibility criteria: 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 normal)
* Pregnancy

Primary outcomes:
measure: BMI
timeFrame: 6 months
measure: Serum Uric Acid
timeFrame: 6 months
measure: Serum Creatinine
timeFrame: 6 months
measure: Ambulatory Systolic Blood Pressure
timeFrame: 6 months
measure: Ambulatory Diastolic Blood Pressure
timeFrame: 6 months
measure: Serum Glucose
timeFrame: 6 months
measure: Serum Insulin
timeFrame: 6 months
measure: Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment)
timeFrame: 6 months
measure: Seum Total Cholesterol
timeFrame: 6 months
measure: Serum HDL-cholesterol
timeFrame: 6 months
measure: Serum Triglycerides
timeFrame: 6 months
measure: Urine Uric Acid
timeFrame: 6 months
measure: Urine Creatinine
timeFrame: 6 months
measure: Fractional Excretion UA
timeFrame: 6 months
measure: Urine pH
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Naim M Maalouf, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marin M, Maalouf NM. Effects of pharmacological reversal of hyperuricemia on features of the metabolic syndrome in patients with gouty arthritis. J Investig Med. 2018 Oct;66(7):1031-1036. doi: 10.1136/jim-2018-000728. Epub 2018 Apr 4.