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Completed

NCT Number: NCT01931527

Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Rasburicase

Drug

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

Other names: Elitek

Primary outcomes

  1. Percent Increase in Insulin-stimulated Glucose Uptake

    Time frame: 12 hours after reducing uric acid

    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.

Secondary outcomes

  1. The Effect of Reducing Uric Acid on Oxidative Status

    Time frame: 12 hours after reducing uric acid

    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.

  2. Baseline Carbonylated Protein Ratio

    Time frame: Before reducing uric acid

    Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle

  3. AFTER Rasburicase Carbonylated Protein Ratio

    Time frame: 12 hours after reducing uric acid

    Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle

  4. Baseline Plasma TRAP

    Time frame: Before reducing uric acid

    Total Radical-Trapping Antioxidant Potential

  5. AFTER Rasburicase Plasma TRAP

    Time frame: 12 hours after reducing uric acid

    Total Radical-Trapping Antioxidant Potential

  6. Baseline Plasma FRAP

    Time frame: Before reducing uric acid

    Ferric-Reducing Antioxidant Potential

  7. AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹)

    Time frame: 12 hours after reducing uric acid

    Ferric-Reducing Antioxidant Potential

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Official study title

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

Acronym: UA

Important dates

Study start
2006
Primary completion
2008
Study completion
2012
First posted
Aug 29, 2013
Registry last updated
Aug 14, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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