Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01654276
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: Febuxostat	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Pharmacological Reversal of Hyperuricemia on Features of the Metabolic Syndrome
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. BMI [6 months]

2. Serum Uric Acid [6 months]

3. Serum Creatinine [6 months]

4. Ambulatory Systolic Blood Pressure [6 months]

   Systolic BP by ambulatory blood pressure monitor.

5. Ambulatory Diastolic Blood Pressure [6 months]

   Diastolic BP by ambulatory blood pressure monitor.

6. Serum Glucose [6 months]

7. Serum Insulin [6 months]

8. Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment) [6 months]

9. Seum Total Cholesterol [6 months]

10. Serum HDL-cholesterol [6 months]

11. Serum Triglycerides [6 months]

12. Urine Uric Acid [6 months]

13. Urine Creatinine [6 months]

14. Fractional Excretion UA [6 months]

15. Urine pH [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	UT Southwestern Medical Center	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Naim Maalouf, Assistant Professor of Medicine, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01654276
• Other Study ID Numbers: MSA-FEB-137
• First Posted: Jul 31, 2012
• Last Update Posted: Jun 18, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Metabolic Syndrome; Hyperuricemia; Febuxostat

Study Results

Participant Flow

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Period Title: Overall Study
STARTED	24
Visit 2 (2 Months)	19
Visit 3 (4 Months)	18
Visit 4 (6months)	18
COMPLETED	18
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (8)
Sex: Female, Male (Count of Participants)
Female	6 25%
Male	18 75%

Outcome Measures

1. Primary Outcome

Title	BMI
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [kg/m^2]	33.4 (5.9)

2. Primary Outcome

Title	Serum Uric Acid
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	4.4 (1.1)

3. Primary Outcome

Title	Serum Creatinine
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	0.98 (0.22)

4. Primary Outcome

Title	Ambulatory Systolic Blood Pressure
Description	Systolic BP by ambulatory blood pressure monitor.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mmHg]	126 (14)

5. Primary Outcome

Title	Ambulatory Diastolic Blood Pressure
Description	Diastolic BP by ambulatory blood pressure monitor.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mmHg]	75 (9)

6. Primary Outcome

Title	Serum Glucose
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	107 (30)

7. Primary Outcome

Title	Serum Insulin
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mU/L]	14 (6.1)

8. Primary Outcome

Title	Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [Homeostatic model assessment for Insulin]	1.86 (.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gout and Hyperuricemia
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	t-test, 2 sided
	Comments

9. Primary Outcome

Title	Seum Total Cholesterol
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	196 (46)

10. Primary Outcome

Title	Serum HDL-cholesterol
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	49 (16)

11. Primary Outcome

Title	Serum Triglycerides
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	175 (107)

12. Primary Outcome

Title	Urine Uric Acid
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	208 (137)

13. Primary Outcome

Title	Urine Creatinine
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [mg/dl]	1332 (669)

14. Primary Outcome

Title	Fractional Excretion UA
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [% of serum uric acid excreted in urine]	0.04 (0.02)

15. Primary Outcome

Title	Urine pH
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
Measure Participants	18
Mean (Standard Deviation) [pH]	5.58 (0.43)

Adverse Events

Time Frame	6 months
Arm/Group Title	Gout and Hyperuricemia
Arm/Group Description	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. Febuxostat: One 40 mg tablet once a day for 6 months
All Cause Mortality
	Gout and Hyperuricemia
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gout and Hyperuricemia
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Hepatobiliary disorders
Abnormal Liver Function Test	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Gout and Hyperuricemia
	Affected / at Risk (%)	# Events
Total	0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.