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The purpose of this study is to learn more about what is the effect of uric acid on oxidative stress and on the way the body metabolizes sugar in obese people. Understanding this may lead to better diseases such as diabetes.
It has been hypothesized that oxidative stress is involved in the pathogenesis of insulin resistance associated with obesity. Circulating uric acid (UA) is the body's major endogenous plasma antioxidant. Therefore, the investigators evaluated whether alterations in serum UA concentration affect: 1) systemic and skeletal muscle oxidative stress, 2) total antioxidant capacity, and 4) skeletal muscle insulin sensitivity during a hyperinsulinemic-euglycemic clamp.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Obese subjects with normal uric acid | No Intervention | Subjects with a body mass index = or > 30 kg/m² with normal uric acid (= or < 5 mg/dL) | |
| Obese subjects with high uric acid | Experimental | Subjects with a body mass index = or > 30 kg/m² with high uric acid (>6 mg/dL) Intervention: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rasburicase | Drug | one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Increase in Insulin-stimulated Glucose Uptake | Uric acid will be reduced to 0 with a 30 minute infusion of a uricase (Elitek, Sanofi-Aventis). A hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope glucose tracer infusion will be used to measure percent increase in insulin-stimulated glucose uptake in obese subjects with high uric acid before and after uric acid reduction. | 12 hours after reducing uric acid |
| Measure | Description | Time Frame |
|---|---|---|
| The Effect of Reducing Uric Acid on Oxidative Status | Uric acid will be reduced to 0 with a 30 minute infusion of a uricase (Elitek, Sanofi-Aventis). Systemic (urinary isoprostanes) and skeletal muscle (carbonylated protein ratio) oxidative stress and total antioxidant capacity (plasma TRAP and FRAP) will be measured in obese subjects with high uric acid before and after uric acid reduction. Levels of isoprostanes were normalized to urinary creatinine and reported at ng/mg. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Samuel Klein, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Obese Subjects With Normal Uric Acid | Subjects with a body mass index = or > 30 kg/m2 with normal uric acid (= or < 5 mg/dL) |
| FG001 | Obese Subjects With High Uric Acid | Subjects with a body mass index = or > 30 kg/m2 with high uric acid (>6 mg/dL) Intervention: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min Rasburicase: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Obese subjects with low uric acid (<5mg/dL)
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Uric Acid | 16 obese subjects (BMI 37.1±0.7 kg/m2) with uric acid <5mg/dL |
| BG001 | High Uric Acid | 15 obese subjects (BMI 37.1±0.7 kg/m2) with uric acid >6mg/dL |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Increase in Insulin-stimulated Glucose Uptake | Uric acid will be reduced to 0 with a 30 minute infusion of a uricase (Elitek, Sanofi-Aventis). A hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope glucose tracer infusion will be used to measure percent increase in insulin-stimulated glucose uptake in obese subjects with high uric acid before and after uric acid reduction. | Posted | Mean | Standard Error | % incr. in insulin-mediated gluc. uptake | 12 hours after reducing uric acid |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Obese Subjects With Normal Uric Acid | Subjects with a body mass index = or > 30 kg/m2 with normal uric acid (= or < 5 mg/dL) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elisa Fabbrini, MD, PhD | Washington University School of Medicine | 314-362-8156 | efabbrini@dom.wustl.edu |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D024821 | Metabolic Syndrome |
| D033461 | Hyperuricemia |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C469709 | rasburicase |
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| 12 hours after reducing uric acid |
| Baseline Carbonylated Protein Ratio | Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle | Before reducing uric acid |
| AFTER Rasburicase Carbonylated Protein Ratio | Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle | 12 hours after reducing uric acid |
| Baseline Plasma TRAP | Total Radical-Trapping Antioxidant Potential | Before reducing uric acid |
| AFTER Rasburicase Plasma TRAP | Total Radical-Trapping Antioxidant Potential | 12 hours after reducing uric acid |
| Baseline Plasma FRAP | Ferric-Reducing Antioxidant Potential | Before reducing uric acid |
| AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹) | Ferric-Reducing Antioxidant Potential | 12 hours after reducing uric acid |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body mass index | Mean | Standard Deviation | kg/m2 |
|
| Plasma uric acid concentration | Mean | Standard Deviation | mg/dL |
|
Subjects with a body mass index = or > 30 kg/m^2 with high uric acid (>6 mg/dL)
Intervention: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min
Rasburicase: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min
|
|
| Secondary | The Effect of Reducing Uric Acid on Oxidative Status | Uric acid will be reduced to 0 with a 30 minute infusion of a uricase (Elitek, Sanofi-Aventis). Systemic (urinary isoprostanes) and skeletal muscle (carbonylated protein ratio) oxidative stress and total antioxidant capacity (plasma TRAP and FRAP) will be measured in obese subjects with high uric acid before and after uric acid reduction. Levels of isoprostanes were normalized to urinary creatinine and reported at ng/mg. | Posted | Mean | Standard Error | ng/mg | 12 hours after reducing uric acid |
|
|
|
| Secondary | Baseline Carbonylated Protein Ratio | Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle | Posted | Mean | Standard Error | Ratio | Before reducing uric acid |
|
|
|
| Secondary | AFTER Rasburicase Carbonylated Protein Ratio | Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle | Analysis only completed on subjects in the High Uric Acid group | Posted | Mean | Standard Error | Ratio | 12 hours after reducing uric acid |
|
|
|
| Secondary | Baseline Plasma TRAP | Total Radical-Trapping Antioxidant Potential | Posted | Mean | Standard Error | mmol · Lˉ¹ | Before reducing uric acid |
|
|
|
| Secondary | AFTER Rasburicase Plasma TRAP | Total Radical-Trapping Antioxidant Potential | AFTER rasburicase plasma Total Radical-Trapping Antioxidant Potential (TRAP) was only measured in the subjects with high uric acid | Posted | Mean | Standard Error | mmol · Lˉ¹ | 12 hours after reducing uric acid |
|
|
|
| Secondary | Baseline Plasma FRAP | Ferric-Reducing Antioxidant Potential | Posted | Mean | Standard Error | mmol Fe⁺² · Lˉ¹ | Before reducing uric acid |
|
|
|
| Secondary | AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹) | Ferric-Reducing Antioxidant Potential | AFTER rasburicase plasma FRAP only measured in subjects with high uric acid | Posted | Mean | Standard Error | mmol Fe⁺² · Lˉ¹ | 12 hours after reducing uric acid |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| EG001 | Obese Subjects With High Uric Acid | Subjects with a body mass index = or > 30 kg/m2 with high uric acid (>6 mg/dL) Intervention: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min Rasburicase: one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min | 0 | 15 | 0 | 15 |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D010335 | Pathologic Processes |