Trial Outcomes & Findings for Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status (NCT NCT01931527)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

31 participants

Primary outcome timeframe

12 hours after reducing uric acid

Results posted on

2018-08-14

Participant Flow

Participant milestones

Participant milestones
Measure	Obese Subjects With Normal Uric Acid Subjects with a body mass index = or \> 30 kg/m2 with normal uric acid (= or \< 5 mg/dL)	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
Overall Study STARTED	16	15
Overall Study COMPLETED	16	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Reducing Uric Acid on Insulin Sensitivity and Oxidative Status

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Uric Acid n=16 Participants 16 obese subjects (BMI 37.1±0.7 kg/m2) with uric acid \<5mg/dL	High Uric Acid n=15 Participants 15 obese subjects (BMI 37.1±0.7 kg/m2) with uric acid \>6mg/dL	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants
Body mass index	35.9 kg/m2 STANDARD_DEVIATION 3.2 • n=5 Participants	38.3 kg/m2 STANDARD_DEVIATION 4.8 • n=7 Participants	37.1 kg/m2 STANDARD_DEVIATION 4.1 • n=5 Participants
Plasma uric acid concentration	4.5 mg/dL STANDARD_DEVIATION 0.2 • n=5 Participants	7.1 mg/dL STANDARD_DEVIATION 1.6 • n=7 Participants	5.7 mg/dL STANDARD_DEVIATION 1.7 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid n=16 Participants Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
Percent Increase in Insulin-stimulated Glucose Uptake BASAL Insulin Sensitivity	231 % incr. in insulin-mediated gluc. uptake Standard Error 23	162 % incr. in insulin-mediated gluc. uptake Standard Error 24
Percent Increase in Insulin-stimulated Glucose Uptake AFTER RASBURICASE Insulin Sensitivity	NA % incr. in insulin-mediated gluc. uptake Standard Error NA Rasburicase infusion to lower uric acid was only administered to subjects in the High Uric Acid group	156 % incr. in insulin-mediated gluc. uptake Standard Error 17

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid n=16 Participants Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
The Effect of Reducing Uric Acid on Oxidative Status BASELINE urinary isoprostanes	1.0 ng/mg Standard Error 0.15	0.68 ng/mg Standard Error 0.07
The Effect of Reducing Uric Acid on Oxidative Status AFTER RASBURICASE isoprostanes	NA ng/mg Standard Error NA Rasburicase infusion to reduce uric acid was administered only to the High Uric Acid group	0.96 ng/mg Standard Error 0.12

SECONDARY outcome

Timeframe: Before reducing uric acid

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

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid n=16 Participants Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
Baseline Carbonylated Protein Ratio	929 Ratio Standard Error 86	680 Ratio Standard Error 56

SECONDARY outcome

Timeframe: 12 hours after reducing uric acid

Population: Analysis only completed on subjects in the High Uric Acid group

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

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
AFTER Rasburicase Carbonylated Protein Ratio	—	1085 Ratio Standard Error 131

SECONDARY outcome

Timeframe: Before reducing uric acid

Total Radical-Trapping Antioxidant Potential

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid n=16 Participants Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
Baseline Plasma TRAP	1.11 mmol · Lˉ¹ Standard Error 0.02	1.31 mmol · Lˉ¹ Standard Error 0.05

SECONDARY outcome

Timeframe: 12 hours after reducing uric acid

Population: AFTER rasburicase plasma Total Radical-Trapping Antioxidant Potential (TRAP) was only measured in the subjects with high uric acid

Total Radical-Trapping Antioxidant Potential

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
AFTER Rasburicase Plasma TRAP	—	0.71 mmol · Lˉ¹ Standard Error 0.02

SECONDARY outcome

Timeframe: Before reducing uric acid

Ferric-Reducing Antioxidant Potential

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid n=16 Participants Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
Baseline Plasma FRAP	1.03 mmol Fe⁺² · Lˉ¹ Standard Error 0.02	1.39 mmol Fe⁺² · Lˉ¹ Standard Error 0.05

SECONDARY outcome

Timeframe: 12 hours after reducing uric acid

Population: AFTER rasburicase plasma FRAP only measured in subjects with high uric acid

Ferric-Reducing Antioxidant Potential

Outcome measures

Outcome measures
Measure	Obese Subjects With Normal Uric Acid Subjects with a body mass index = or \> 30 kg/m\^2 with normal uric acid (= or \< 5 mg/dL)	Obese Subjects With High Uric Acid n=15 Participants 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
AFTER Rasburicase Plasma FRAP (Fe⁺² · Lˉ¹)	—	0.42 mmol Fe⁺² · Lˉ¹ Standard Error 0.02

Adverse Events

Obese Subjects With Normal Uric Acid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Obese Subjects With High Uric Acid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Elisa Fabbrini, MD, PhD

Washington University School of Medicine

Phone: 314-362-8156

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place