Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome

This study is currently recruiting participants.
Verified July 2012 by University of Texas Southwestern Medical Center
Sponsor:
Information provided by (Responsible Party):
Naim Maalouf, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01654276
First received: June 28, 2012
Last updated: July 30, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Gout
Drug: Febuxostat
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Pharmacological Reversal of Hyperuricemia on Features of the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Insulin sensitivity measured by HOMA (HOmeostasis Model Assessment) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ambulatory Blood Pressure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Fasting serum glucose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Fasting serum triglycerides [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Fasting serum HDL-cholesterol [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Fasting urine pH [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gout and hyperuricemia
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 Name: Uloric

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01654276

Contacts
Contact: Naim M Maalouf, MD 2146482954 naim.maalouf@utsouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-8885
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Naim M Maalouf, MD UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: Naim Maalouf, Assistant Professor of Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01654276     History of Changes
Other Study ID Numbers: MSA-FEB-137
Study First Received: June 28, 2012
Last Updated: July 30, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Metabolic Syndrome X
Hyperuricemia
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pathologic Processes
Febuxostat
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014