Uric Acid and the Endothelium in CKD

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01228903

Enrollment

Registered

2010-10-27

Start date

2010-10-31

Completion date

2016-09-30

Last updated

2017-06-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Disease

Keywords

uric acid kidney disease endothelial dysfunction

Brief summary

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

Detailed description

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.

Interventions

DRUGAllopurinol

Xanthine oxidase inhibitor- effective at lowering uric acid levels.

OTHERPlacebo

Placebo tablets with no active ingredient

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	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

Other

Measure	Time frame	Description
Change in Serum Uric Acid Levels From Baseline to Week 12	Baseline and 12 weeks	Serum uric acid levels were measured both at baseline and after 12 weeks

Countries

United States

Participant flow

Participants by arm

Arm	Count
Control 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. Placebo: Placebo tablets with no active ingredient	41
Allopurinol 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. Allopurinol: Xanthine oxidase inhibitor- effective at lowering uric acid levels.	39
Total	80

Baseline characteristics

Characteristic	Control	Allopurinol	Total
Age, Continuous	58.9 years STANDARD_DEVIATION 9.3	55.9 years STANDARD_DEVIATION 13.7	57.4 years STANDARD_DEVIATION 11.5
Region of Enrollment United States	41 participants	39 participants	80 participants
Sex: Female, Male Female	9 Participants	7 Participants	16 Participants
Sex: Female, Male Male	32 Participants	32 Participants	64 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	9 / 41	4 / 39
serious Total, serious adverse events	0 / 41	1 / 39