Role of the Endothelium in Stroke-like Episode Among CDG Patients

Not Applicable

Completed

• Conditions: Congenital Disorders of Glycosylation
• Interventions: Biological: Peripheral blood puncture

• Registration Number: NCT03250728
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The aim of the study is to evaluate the role of the endothelial barrier in the occurrence of stroke-like episode. And to study the protein C system on the surface of the endothelium.

Detailed Description

The study consists in isolating endothelial progenitor cells in peripheral blood. After blood puncture, PBMC (peripheral blood mononuclear cell) are isolated by Ficoll gradient and then culturing in appropriated medium.

When cells are confluent, investigators can study the endothelial barrier by using permeability assay and transendothelial resistance test (iCELLigence technology).

Then, protein C system will be studied. Indeed, EPCR (Endothelial protein C receptor) and TM (thrombomodulin), are the two receptors responsible for the activation of protein C. The expression of these receptors will be assessed in flow cytometry. The activated protein C is able to interact with the third receptor PAR1 (Protease activated receptor 1) which is responsible for the protective effects of the on the endothelial barrier. The PAR1 expression will be studied in flow cytometry also.

In order to measure the capacity of the protein C system to generate activated protein C investigators will assay an activated protein C generation on the cell surface.

All these assays will be realized in basal condition and in heat stress (42°C), to mimic the stroke-like episode environment. Indeed, stroke-like episodes occur always during febrile illness.

Study Timeline

• Study First Submitted: 2017-08-11
• Study First Submitted QC: 2017-08-11
• Study First Posted: 2017-08-16
• Study Start: 2017-11-23
• Primary Completion: 2019-04-26
• Study Completion: 2019-04-26
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-07
• Last Update Posted: 2020-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• patients with CDG molecularly diagnosed
• with stroke-like history or not

Exclusion Criteria

• rejection to participate in research

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CDG with stroke-like history	Peripheral blood puncture	-
CDG without stroke-like history	Peripheral blood puncture	-

Primary Outcome Measures

Name	Time	Method
Endothelial permeability assay in basal condition	at inclusion
Endothelial permeability assay after an heat shock	at inclusion

Secondary Outcome Measures

Name	Time	Method
Quantification of the endothelial receptors (EPCR, TM, PAR1)	at inclusion
Endothelial permeability assay after an activated protein C incubation	at inclusion
Activated protein C generation assay on the endothelial cell surface	at inclusion

Trial Locations

Locations (1)

Hopital Necker enfants malades; 🇫🇷 Paris, France