Uric Acid and the Endothelium in CKD

Study Overview
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Brief Summary
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This study will test the hypothesis that uric acid impairs the function of vessels in patients with kidney disease

Detailed Description
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The purpose of the study is to understand the effect of lowering serum uric acid levels on vascular function in individuals with chronic kidney disease by comparing the effects of: 1) Allopurinol therapy and 2) Placebo. Patients will receive: 3 month study drug (either allopurinol or placebo), with assessment of serum uric acid levels and vascular function.

Official Title
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Is Uric Acid a Mediator of Endothelial Dysfunction in Patients With Chronic Kidney Disease?

Conditions
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Kidney Disease

Intervention / Treatment
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* Drug: Allopurinol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with moderate chronic kidney disease (CKD stage III) with estimated glomerular filtration rates between 30-60 mL/min/ 1.73m2 Elevated uric acid levels Age range: more than 18 years old Ability to give informed consent Albumin > 3.0 g/dL BMI < 40 kg/m2 Exclusion Criteria: Life expectancy < 1.0 years Expected to undergo living related kidney transplant in 6 months Pregnant, breast feeding, or unwilling to use adequate birth control History of severe liver disease History of severe congestive heart failure History of hospitalizations within 3 months Active infection, on antibiotics History of Warfarin Use or other medications that are contraindicated with allopurinol Uncontrolled hypertension History of acute gout on Allopurinol History of adverse reaction to Allopurinol Immunosuppressive therapy within the last 1 yr

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Patients who are randomized to this group will received placebo tablets. Placebo tables do not contain an active ingredient. This group will be used as a baseline group to compare the effects of lowering uric acid on vascular function. | Other: Placebo<br>* Placebo tablets with no active ingredient<br>|
| Active Comparator: Allopurinol<br>Patients who are randomized to this group will receive allopurinol tablets. Allopurinol is a medicine that lowers uric acid levels. The effects of lowering uric acid on vascular function outcomes will be assessed and compared to the control group. | Drug: Allopurinol<br>* Xanthine oxidase inhibitor- effective at lowering uric acid levels.<br>* Other names: Zyloprim, Allohexal, Allosig, Milurit, Alloril, Progout, Zyloric.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endothelial Dependent Dilation From Baseline to Week 12 | Change in Endothelial Dependent Dilation measured by Flow Mediated Dilation at baseline and week 12 | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in C-reactive Protein From Baseline to Week 12 |  | Baseline and 12 weeks | 
| Change in Serum Interleukin-6 From Baseline to Week 12 |  | Baseline and 12 weeks | 
| Change in Monocyte Chemotactic Protein-1 From Baseline to Week 12 |  | Baseline and 12 weeks | 
| Change in Oxidized Low Density Lipoprotein From Baseline to Week 12 |  | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uric acid kidney disease endothelial dysfunction