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Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status (UA)

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ClinicalTrials.gov Identifier: NCT01931527
Recruitment Status : Completed
First Posted : August 29, 2013
Results First Posted : May 15, 2015
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Obesity Metabolic Syndrome Hyperuricemia Drug: Rasburicase Not Applicable

Detailed 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effect of Plasma Uric Acid on Insulin Sensitivity, Endothelial Function and Inflammation
Study Start Date : July 2006
Actual Primary Completion Date : June 2008
Actual Study Completion Date : November 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
No Intervention: Obese subjects with normal uric acid
Subjects with a body mass index = or > 30 kg/m² with normal uric acid (= or < 5 mg/dL)
Experimental: 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

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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01931527


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Samuel Klein, MD Washington University School of Medicine
More Information
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01931527    
Other Study ID Numbers: 06-0509 / 201104189
First Posted: August 29, 2013    Key Record Dates
Results First Posted: May 15, 2015
Last Update Posted: August 14, 2018
Last Verified: July 2018
Keywords provided by Washington University School of Medicine:
Obesity
Metabolic syndrome
Hyperuricemia
Additional relevant MeSH terms:
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Metabolic Syndrome
Insulin Resistance
Hyperuricemia
Pathologic Processes
Hyperinsulinism
 Glucose Metabolism Disorders
Metabolic Diseases
Rasburicase
Gout Suppressants
Antirheumatic Agents