Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status

Obesity Clinical Trial

— UA  

Official title:

Effect of Plasma Uric Acid on Insulin Sensitivity, Endothelial Function and Inflammation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01931527
• Other study ID #: 06-0509 / 201104189
• Status: Completed
• Phase: N/A
• Start date: July 2006
• Est. completion date: November 2012

Study information

• Verified date: July 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: November 2012
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• obese (BMI 30-45 kg/m²);

• serum UA concentration either =5 mg/dL or =4.0 mg/dL (297 µmol/L)],

Exclusion Criteria:

• renal dysfunction (serum creatinine >1.5 mg/dL);

• pregnancy or lactating;

• take urate-lowering agents, thiazide diuretics, prednisone or medications containing aspirin or other salicylates;

• history of xanthinuria, type 2 diabetes or other significant organ system dysfunction;

• have G6PD deficiency;

• use hormone-replacement or oral-contraceptive therapy;

• smoke tobacco;

• anemic (Hb <10 g/dl)

Related Conditions & MeSH terms

• Hyperuricemia
• Insulin Resistance
• Metabolic Syndrome
• Metabolic Syndrome X
• Obesity

Intervention

Drug:
• Rasburicase
one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12 hours after reducing uric acid
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.	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	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	12 hours after reducing uric acid
Secondary	Baseline Plasma TRAP	Total Radical-Trapping Antioxidant Potential	Before reducing uric acid
Secondary	AFTER Rasburicase Plasma TRAP	Total Radical-Trapping Antioxidant Potential	12 hours after reducing uric acid
Secondary	Baseline Plasma FRAP	Ferric-Reducing Antioxidant Potential	Before reducing uric acid
Secondary	AFTER Rasburicase Plasma FRAP (Fe?² · L¯¹)	Ferric-Reducing Antioxidant Potential	12 hours after reducing uric acid