Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: Febuxostat

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-8885
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Febuxostat; 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; One 40 mg tablet once a day for 6 months; 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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Naim M Maalouf, MD, UT Southwestern Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 28, 2012
• First Submitted That Met QC Criteria: July 30, 2012
• First Posted (Estimate): July 31, 2012

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Hyperuricemia; Antirheumatic Agents; Gout Suppressants; Febuxostat
• Other Study ID Numbers: MSA-FEB-137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO