Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome

Study Overview
=================
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.

Official Title
-----------------
Effects of Pharmacological Reversal of Hyperuricemia on Features of the Metabolic Syndrome

Conditions
-----------------
Gout

Intervention / Treatment
-----------------
* Drug: Febuxostat


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Febuxostat<br>Adult patients (age > 21 years) with gout and hyperuricemia (serum uric acid > 7.0 mg/dl in men and >6.0 mg/dl in women) requiring uric acid lowering therapy. | Drug: Febuxostat<br>* One 40 mg tablet once a day for 6 months<br>* Other names: Uloric;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI |  | 6 months | 
| Serum Uric Acid |  | 6 months | 
| Serum Creatinine |  | 6 months | 
| Ambulatory Systolic Blood Pressure | Systolic BP by ambulatory blood pressure monitor. | 6 months | 
| Ambulatory Diastolic Blood Pressure | Diastolic BP by ambulatory blood pressure monitor. | 6 months | 
| Serum Glucose |  | 6 months | 
| Serum Insulin |  | 6 months | 
| Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment) |  | 6 months | 
| Seum Total Cholesterol |  | 6 months | 
| Serum HDL-cholesterol |  | 6 months | 
| Serum Triglycerides |  | 6 months | 
| Urine Uric Acid |  | 6 months | 
| Urine Creatinine |  | 6 months | 
| Fractional Excretion UA |  | 6 months | 
| Urine pH |  | 6 months |