NCT03395977

Uric Acid Effects on Endothelium and Oxydative Stress

Completed NA Last updated 28 February 2020

What this trial tests

NA trial testing Placebos in Oxidative Stress in 53 participants. Completed in 27 February 2020.

Timeline

3 January 2018

Primary endpoint
31 December 2019

27 February 2020

Quick facts

Lead sponsor	Erasme University Hospital
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	basic science
Enrollment	53
Start date	3 January 2018
Primary completion	31 December 2019
Estimated completion	27 February 2020
Sites	1 location across Belgium

Drugs / interventions tested

• Placebos — full drug profile →
• Febuxostat (FEBUXOSTAT) — full drug profile →
• Rasburicase — full drug profile →

Conditions studied

• Oxidative Stress — all drugs for Oxidative Stress →
• Endothelial Function — all drugs for Endothelial Function →
• Cardiovascular System — all drugs for Cardiovascular System →
• Hypertension — all drugs for Hypertension →

Sponsor

Erasme University Hospital

Who can join

Adults 18 to 65, any sex, with Oxidative Stress or Endothelial Function. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Cardiovascular disease is the leading cause of mortality worldwide. Endothelial dysfunction (ED) is the main mechanism which leads to atherosclerosis, where the balance between pro and antioxidant factors results in a decreased nitric oxide (NO) bioavailability. Xanthine OxidoReductase (XOR) is one of the main generators of reactive oxygen species (ROS). Uric acid (UA), a major antioxidant in human plasma and end product of purine metabolism, is associated with cardiovascular diseases since many years; however the precise mechanisms which relate UA to ED are still not well understood.

The purpose of this study is to unravel the XOR and UA pathways involved in ED. Three groups of participants (young (\< 40 y) male healthy participants \[1\] ; male and female helthy participants (40 to 65 y) \[2\] and patients with primary hypertension \[3\]) will be exposed to febuxostat (a strong and selective XOR inhibitor), or recombinant uricase (which oxidizes UA into allantoin) to vary UA levels and concomitantly control for confounding changes in XOR activity. Oxidative stress will be estimated by several markers. Endothelial function will be assessed by a laser Doppler imager in the presence of hyperthermia and endothelium stimulators. This study is specifically designed to untie the respective effects of UA and XOR pathways on oxidative stress and endothelial function in humans.

The investigators will test the following hypothesis:

1. An extremely low level of uric acid after uricase administration induces endothelial dysfunction and oxydative stress,
2. A specific XO inhibitor limits unfavourable effects of the serum UA reduction elicited by uricase administration,
3. Endothelial function and oxydative stress are further improved with febuxostat as compared to placebo,
4. All these observations are more marked in hypertensives then in older participants than in young healthy subjects.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Severe Hypouricemia Impairs Endothelium-Dependent Vasodilatation and Reduces Blood Pressure in Healthy Young Men: A Randomized, Placebo-Controlled, and Crossover Study.
   De Becker B, Coremans C, Chaumont M, Delporte C, et al · · 2019 · cited 30× · PMID 31752638 · DOI 10.1161/jaha.119.013130
2. Acute effects of hypouricemia on endothelium, oxidative stress, and arterial stiffness: A randomized, double-blind, crossover study.
   De Becker B, Hupkens E, Dewachter L, Coremans C, et al · · 2021 · cited 8× · PMID 34435469 · DOI 10.14814/phy2.15018
3. Serum uric acid: a futile bystander in endothelial function?
   De Becker B, Van De Borne P. · · 2023 · cited 5× · PMID 37470459 · DOI 10.1080/08037051.2023.2237123