Evaluation of Endothelial Dysfunction Using the "Flow Mediated Dilation" Test in a Population of Chronic Renal Failure Patients at Different Stages, and Evaluation of the Role of Antiphospholipid Antibodies

NCT ID: NCT06347029

Last Updated: 2024-04-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-17

Study Completion Date

2024-12-31

Brief Summary

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The vascular endothelium is an organ in its own right, playing, among other things, a primordial role in the control of vascular tone. This vascular tone is ensured by pro-dilator mediators (nitric oxide (NO), prostacyclins (PGI2)), or vasoconstrictors (endothelin, thromboxane A2 or PGH2).Uremic toxin accumulation in chronic kidney disease (CKD) is a well-known factor in endothelial dysfunction, often associated with higher cardiovascular risk. This association is also present for terminal chronic kidney disease characterized by the need to resort to an extra-renal purification technique (in-center hemodialysis (HD), daily home hemodialysis (HDQ), peritoneal dialysis) or to resort to renal transplantation.

For HD to be effective, it is essential that the blood flow rate passing through the dialyzer is greater than 300ml/min. This imperative requires that any hemodialysis patient have specific vascular access (dialysis catheter or arteriovenous fistula (AVF)) to ensure these flow rates. The vascular access of choice is the arteriovenous fistula , because it is associated with a lower risk of infection and lower morbidity and mortality. Making an arteriovenous fistula consists of surgically creating an anastomosis between a vein and an artery.

Complications of arteriovenous fistula are common. Arteriovenous fistula maturation may be delayed (maturation delay) or even absent. Drainage veins and/or anastomoses can also be the site of stenosis or thrombosis. The pathophysiology of these complications is complex and multifactorial. Among the risk factors for these complications (delay or absence of maturation, stenosis thrombosis), the positivity of antiphospholipid antibodies (aPL) can be cited, as well as endothelial dysfunction.

Antiphospholipid syndrome (APS) is an autoimmune disease causing a thrombotic phenotype. This is an acquired thrombophilia. In the general population, the prevalence of antiphospholipid antibodies is around 0.5%; this prevalence is far from rare in hemodialysis, since it represents up to 37% in dialysis patients. In a retrospective study carried out at Brugmann University Hospital in 2023 , on 115 patients with AVF and in whom aPL dosages were available, the prevalence of persistent positivity (2 positive dosages spaced more than 12 weeks apart) was 21%.

Interestingly, a third of the cohort presented an antibody profile that did not allow them to be classified according to the classification criteria in force. This group corresponds to patients with a single positive dosage, either not recontrolled or recontrolled negative. This group was called Fluctuating. This fluctuating group was associated with arteriovenous fistula complications in a 2019 study.

Endothelial dysfunction is also implicated in the pathophysiology of APS. In clinical practice, the "flow mediated dilation" (FMD) test makes it possible to assess endothelial dysfunction in vivo. It involves the phenomenon of post-occlusive hyperemia which is mainly linked to NO and endothelium-dependent vasodilation. In the brachial artery, NO is the sole mediator of FMD. Endothelial dysfunction according to FMD has been described in populations with advanced chronic kidney disease, as well as patients with cardiovascular diseases. Hemodialysis patients with delayed/absence of arteriovenous fistula maturation have more pathological FMDs compared to dialysis patients without fistula problems. However, the additive role of aPL in this different population has not been studied in terms of endothelial dysfunction by FMD.

The objective of this study is to evaluate the weight of antiphospholipid biology on endothelial dysfunction in hemodialysis patients, using the FMD test.

1. Compare endothelial dysfunction by FMD according to the stage of chronic kidney disease and in comparison to a control group without chronic kidney disease.
2. Characterize the FMD pre or post dialysis and according to the duration of the long (for example between Thursday and Sunday) vs. short (between Tuesday and Thursday) inter-dialytic period.
3. Evaluate the relationship between endothelial dysfunction according to FMD, aPL positivity and arteriovenous fistula complications in hemodialysis patients.
4. Evaluate the risk factors associated with endothelial dysfunction according to FMD, and in particular evaluate the impact of antiphospholipid antibodies.
5. Evaluate the correlation between endothelial dysfunction according to FMD and other markers of endothelial dysfunction (urinary NO and metabolites of urinary NO, PGI2, endothelin, PGH2).

Detailed Description

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Conditions

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Chronic Renal Failure

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Chronic kidney disease at stage G3a

Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 60 and 45 ml/min/1.73m²

Group Type EXPERIMENTAL

Urine sampling

Intervention Type PROCEDURE

Urine sampling

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Flow mediated dilatation test

Intervention Type DEVICE

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Chronic kidney disease at stage G3b

Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 45 and 30 ml/min/1.73m²

Group Type EXPERIMENTAL

Urine sampling

Intervention Type PROCEDURE

Urine sampling

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Flow mediated dilatation test

Intervention Type DEVICE

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Chronic kidney disease at stage G4

Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 30 and 15 ml/min/1.73m²

Group Type EXPERIMENTAL

Urine sampling

Intervention Type PROCEDURE

Urine sampling

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Flow mediated dilatation test

Intervention Type DEVICE

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Chronic kidney disease at stage G5 not dialyzed

Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) less than 15 ml/min/1.73m² but not dialyzed

Group Type EXPERIMENTAL

Urine sampling

Intervention Type PROCEDURE

Urine sampling

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Flow mediated dilatation test

Intervention Type DEVICE

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Chronic kidney disease at stage G5 with dialyze

Patients who undergo dialyze

Group Type EXPERIMENTAL

Urine sampling

Intervention Type PROCEDURE

Urine sampling

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Flow mediated dilatation test

Intervention Type DEVICE

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Control

Healthy volunteer patient, without existing kidney disease

Group Type ACTIVE_COMPARATOR

Urine sampling

Intervention Type PROCEDURE

Urine sampling

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Flow mediated dilatation test

Intervention Type DEVICE

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Interventions

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Urine sampling

Urine sampling

Intervention Type PROCEDURE

Blood sampling

Blood sampling

Intervention Type PROCEDURE

Flow mediated dilatation test

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Patients with Chronic kidney disease from stage G3a to G5
* Healthy volunteers

Exclusion Criteria

* Patients with chronic kidney disease stage G5 with no dosage available of antiphospholipid antibodies.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Brugmann University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Tatiana Besse-Hammer

Head of clinical trial unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Brugmann University Hospital

Brussels, , Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Maxime Taghavi

Role: CONTACT

003224772644

Facility Contacts

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Maxime Taghavi, MD PhD

Role: primary

Other Identifiers

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Endothelial dysfunction

Identifier Type: -

Identifier Source: org_study_id

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