Uric Acid Effects on Endothelium and Oxydative Stress

Launched by ERASME UNIVERSITY HOSPITAL · Jan 4, 2018

Keywords

ClinConnect Summary

The goals of the research protocol are to clearly untie the respective roles of uric acid (UA) and xanthine oxidoreductase (XOR) pathways on endothelial function and oxidative stress in humans.

UA represents the end-product of purine metabolism due to the loss of uricase 15 million years ago in humans. The selective advantage of this mutation could be the strong antioxidant effect of UA (which represents more than 60% of the antioxidant plasmatic capacity). Many recent epidemiological studies have showed a J-shape association between UA levels and cardiovascular risk. An UA level lower tha...

Gender

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Eligibility criteria

• Phase 1 :
• Inclusion Criteria:
• • Age between 18 and 40 years
• • Male
• • Healthy volunteers
• • Non smoker for at least 6 months
• • Uric acid level in normal range (normouricemic group)
• Exclusion Criteria:
• • Any diseases of one of the following systems: cardiovascular, digestive, hormonal, urinary, pulmonary, rheumatic or immune.
• • Smoker, alcoholic
• • Participants should not take any chronic medicine nor vitamins or other antioxidants.
• • A G6PD deficit will be excluded as this is a contraindication to uricase administration (hemolytic anemia).
• Phase 2 :
• Inclusion Criteria:
• • Age between 40 and 65 years
• • Male or female (menopaused)
• • Healthy volunteers
• • Non smoker for at least 6 months
• • Uric acid level in normal range (normouricemic group)
• Exclusion Criteria:
• • Any diseases of one of the following systems: cardiovascular, digestive, hormonal, urinary, pulmonary, rheumatic or immune.
• • Smoker, alcoholic
• • Participants should not take any chronic medicine nor vitamins or other antioxidants.
• • A G6PD deficit will be excluded as this is a contraindication to uricase administration (hemolytic anemia).
• Phase 3 :
• Inclusion Criteria:
• • Age between 40 and 65 years
• • History of hypertension for more than 6 months
• • Non smoker or smoke stopped for at least for 6 months
• Exclusion Criteria:
• • Acute coronary syndrome
• • Heart failure (LVEJ \< 40%)
• • Diabetes
• • Active smoking
• • Gout
• • Chronic kidney disease stage superior to 3a
• • History of cerebrovascular thrombosis
• • Cirrhosis
• • Alcohol consumption more than 3 units/day
• • Participants should not take any chronic medicine nor vitamins or other antioxidants.
• • A G6PD deficit will be excluded as this is a contraindication to uricase administration (hemolytic anemia).
• • The populations of phases 2 and 3 will be enrolled and studied together with subgroups analyses of the results for the status of hypertension, of treatment, age and gender.