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

Primary Purpose

Obesity, Metabolic Syndrome, Hyperuricemia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Rasburicase
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Obesity focused on measuring Obesity, Metabolic syndrome, Hyperuricemia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Obese subjects with normal uric acid

Obese subjects with high uric acid

Arm Description

Subjects with a body mass index = or > 30 kg/m² with normal uric acid (= or < 5 mg/dL)

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Baseline Carbonylated Protein Ratio
Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle
AFTER Rasburicase Carbonylated Protein Ratio
Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle
Baseline Plasma TRAP
Total Radical-Trapping Antioxidant Potential
AFTER Rasburicase Plasma TRAP
Total Radical-Trapping Antioxidant Potential
Baseline Plasma FRAP
Ferric-Reducing Antioxidant Potential
AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹)
Ferric-Reducing Antioxidant Potential

Full Information

First Posted
August 23, 2013
Last Updated
July 16, 2018
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01931527
Brief Title
Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status
Acronym
UA
Official Title
Effect of Plasma Uric Acid on Insulin Sensitivity, Endothelial Function and Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Metabolic Syndrome, Hyperuricemia
Keywords
Obesity, Metabolic syndrome, Hyperuricemia

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Obese subjects with normal uric acid
Arm Type
No Intervention
Arm Description
Subjects with a body mass index = or > 30 kg/m² with normal uric acid (= or < 5 mg/dL)
Arm Title
Obese subjects with high uric acid
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Rasburicase
Other Intervention Name(s)
Elitek
Intervention Description
one single infusion of rasburicase (0.19 mg/kg FFM) infused over 30 min
Primary Outcome Measure Information:
Title
Percent Increase in Insulin-stimulated Glucose Uptake
Description
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.
Time Frame
12 hours after reducing uric acid
Secondary Outcome Measure Information:
Title
The Effect of Reducing Uric Acid on Oxidative Status
Description
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.
Time Frame
12 hours after reducing uric acid
Title
Baseline Carbonylated Protein Ratio
Description
Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle
Time Frame
Before reducing uric acid
Title
AFTER Rasburicase Carbonylated Protein Ratio
Description
Baseline ratio of total carbonylated proteins to the loading control protein Ran in skeletal muscle
Time Frame
12 hours after reducing uric acid
Title
Baseline Plasma TRAP
Description
Total Radical-Trapping Antioxidant Potential
Time Frame
Before reducing uric acid
Title
AFTER Rasburicase Plasma TRAP
Description
Total Radical-Trapping Antioxidant Potential
Time Frame
12 hours after reducing uric acid
Title
Baseline Plasma FRAP
Description
Ferric-Reducing Antioxidant Potential
Time Frame
Before reducing uric acid
Title
AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹)
Description
Ferric-Reducing Antioxidant Potential
Time Frame
12 hours after reducing uric acid

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel Klein, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

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Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status

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