Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome

Gout Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01654276
• Other study ID #: MSA-FEB-137
• Status: Completed
• Phase: Phase 4
• Start date: May 2012
• Est. completion date: March 2015

Study information

• Verified date: February 2023
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

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 normal)

• Pregnancy

Related Conditions & MeSH terms

• Gout
• Hyperuricemia
• Metabolic Syndrome

Intervention

Drug:
• Febuxostat
One 40 mg tablet once a day for 6 months

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

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