Gout
Conditions
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.
Interventions
DRUGFebuxostat
One 40 mg tablet once a day for 6 months
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment) | 6 months | — |
| Seum Total Cholesterol | 6 months | — |
| Serum HDL-cholesterol | 6 months | — |
| Serum Triglycerides | 6 months | — |
| BMI | 6 months | — |
| Serum Uric Acid | 6 months | — |
| Serum Creatinine | 6 months | — |
| Ambulatory Systolic Blood Pressure | 6 months | Systolic BP by ambulatory blood pressure monitor. |
| Ambulatory Diastolic Blood Pressure | 6 months | Diastolic BP by ambulatory blood pressure monitor. |
| Serum Glucose | 6 months | — |
| Serum Insulin | 6 months | — |
| Urine Uric Acid | 6 months | — |
| Urine Creatinine | 6 months | — |
| Fractional Excretion UA | 6 months | — |
| Urine pH | 6 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Febuxostat: One 40 mg tablet once a day for 6 months | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gout and Hyperuricemia |
|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Ambulatory Diastolic Blood Pressure
Diastolic BP by ambulatory blood pressure monitor.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Ambulatory Diastolic Blood Pressure | 75 mmHg | Standard Deviation 9 |
Primary
Ambulatory Systolic Blood Pressure
Systolic BP by ambulatory blood pressure monitor.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Ambulatory Systolic Blood Pressure | 126 mmHg | Standard Deviation 14 |
Primary
BMI
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | BMI | 33.4 kg/m^2 | Standard Deviation 5.9 |
Primary
Fractional Excretion UA
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Fractional Excretion UA | 0.04 % of serum uric acid excreted in urine | Standard Deviation 0.02 |
Primary
Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Insulin Sensitivity Measured by HOMA (HOmeostasis Model Assessment) | 1.86 Homeostatic model assessment for Insulin | Standard Deviation 0.83 |
p-value: 0.66t-test, 2 sided
Primary
Serum Creatinine
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Serum Creatinine | 0.98 mg/dl | Standard Deviation 0.22 |
Primary
Serum Glucose
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Serum Glucose | 107 mg/dl | Standard Deviation 30 |
Primary
Serum HDL-cholesterol
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Serum HDL-cholesterol | 49 mg/dl | Standard Deviation 16 |
Primary
Serum Insulin
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Serum Insulin | 14 mU/L | Standard Deviation 6.1 |
Primary
Serum Triglycerides
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Serum Triglycerides | 175 mg/dl | Standard Deviation 107 |
Primary
Serum Uric Acid
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Serum Uric Acid | 4.4 mg/dl | Standard Deviation 1.1 |
Primary
Seum Total Cholesterol
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Seum Total Cholesterol | 196 mg/dl | Standard Deviation 46 |
Primary
Urine Creatinine
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Urine Creatinine | 1332 mg/dl | Standard Deviation 669 |
Primary
Urine pH
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Urine pH | 5.58 pH | Standard Deviation 0.43 |
Primary
Urine Uric Acid
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gout and Hyperuricemia | Urine Uric Acid | 208 mg/dl | Standard Deviation 137 |