Crossover Clinical Trial, Randomized, Double Blind, Placebo Controlled Trial

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effect of inhibiting xanthine oxidase with allopurinol in patients with chronic kidney disease in asymptomatic hyperuricemia endothelial injury and vascular repair mechanisms.

Detailed Description
-----------------
The purpose of this study is to determine the effect of inhibiting xanthine oxidase with allopurinol in patients with chronic kidney disease in asymptomatic hyperuricemia endothelial injury and vascular repair mechanisms, evaluating the plasma concentration of angiogenic factors, microparticles of endothelial cells and the cell number circulating endothelial progenitor.

Official Title
-----------------
Crossover Clinical Trial, Randomized, Double Blind, Placebo Controlled Trial. Modulation of Cellular Mediators and Repair Endothelial Damage in Patients With Chronic Renal Disease Through Inhibition of Xanthine Oxidase

Conditions
-----------------
Chronic Kidney Disease

Intervention / Treatment
-----------------
* Drug: Allopurinol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients willing and able to give informed consent for participation in the study Ability to understand study procedures and to comply with it for the duration of the study. Subjects of both sexes, the age range between 18 and 70 years old. Serum uric acid above 7 mg / dl. Estimated glomerular filtration rate by MDRD abbreviated formula less than 60 ml / min / 1.73 m2 and above 15 ml / min / 1.73 m2. Stability of renal function (serum creatinine increase without exceeding 50% in the three months before the start of the study). Clinically stable in terms of no hospitalizations of cardiovascular events in the 3 months before the study began. Exclusion Criteria: Drop active in the 60 days prior to study initiation. Use of allopurinol within 60 days preceding baseline Active infections within 30 days prior to baseline. Patients with systemic inflammatory disease Infection with HIV, Hepatitis C and Hepatitis B. History of cancer within 5 years prior to the first dose of study medication Chronic liver disease. Immunosuppressive therapy. Pregnant women, breastfeeding or planning to become pregnant. Allergy or sensitive to allopurinol. Addiction to drugs or alcohol, in the opinion of the investigator, may interfere with compliance with study requirements. Inability or unwillingness of the individual or legal guardian or representative to give written informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Allopurinol<br> | Drug: Allopurinol<br>* Allopurinol<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating endothelial progenitor cells concentration and microparticles derived from endothelial cells | Effect of inhibiting xanthine oxidase with allopurinol in patients with CKD | Data collected after 4 weeks, 8 weeks and 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of oxidative stress | Evaluated through quantification of oxygen-reactive species | After patient visit (0 weeks, 4, 8 and 12 weeks) | 
| Level of micro inflammation | Evaluated through quantification of C-reactive protein, proinflammatory cytokines, CD14+ and CD16+ monocytes | After patient visit (0 weeks, 4, 8 and 12 weeks) | 
| Level of endothelial dysfunction | Endothelium-dependant vasodilation in response to ischemia evaluated through changes in capillar flux using Doppler laser PeriFlux system 5000 | After patient visit (0 weeks, 4, 8 and 12 weeks) | 
| Blood pressure |  | Each visit (0 weeks, 4 weeks, 8 weeks and 12 weeks) for 24 hours | 
| Glomerular filtration ratio | Estimated through MDRD-4 y Cockroft-Gault. | After patient visit (0 weeks, 4 weeks, 8 weeks and 12 weeks) | 
| Microalbuminuria / Proteinuria | Evaluated through albumin/creatinin ratio and protein/creatinine ratio | Daily, using first urine of the day as a sample. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CKD, allopurinol, chronic kidney disease