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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: Allopurinol

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain, 14002
    • Hospital Universitario Reina Sofia de Cordoba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo
ACTIVE_COMPARATOR: Allopurinol	Drug: Allopurinol; Allopurinol

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.

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Investigators: Principal Investigator: Rafael Santamaría, MD, Hospital Universitario Reina Sofia

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 26, 2014
• Primary Completion (ACTUAL): April 29, 2016
• Study Completion (ACTUAL): April 29, 2016

Study Registration Dates

• First Submitted: March 31, 2015
• First Submitted That Met QC Criteria: July 19, 2021
• First Posted (ACTUAL): July 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: chronic kidney disease; CKD; allopurinol
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: PI12/01866