Clinical trial NCT03250728: Role of the Endothelium in Stroke-like Episode Among CDG Patients
Official title: Role of the Endothelium in Stroke-like Episode Among CDG Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Disorders of Glycosylation
Keywords: CDG
Stroke-like
Endothelial progenitor cells (EPCs)
Protein C
Congenital Disorders og Glycosylation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-08-16
Enrollment: 6
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* rejection to participate in research

Primary outcomes:
measure: Endothelial permeability assay in basal condition
timeFrame: at inclusion
measure: Endothelial permeability assay after an heat shock
timeFrame: at inclusion
Secondary outcomes:
measure: Activated protein C generation assay on the endothelial cell surface
timeFrame: at inclusion
measure: Quantification of the endothelial receptors (EPCR, TM, PAR1)
timeFrame: at inclusion
measure: Endothelial permeability assay after an activated protein C incubation
timeFrame: at inclusion
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Necker enfants malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pascale De Lonlay, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Delphine Borgel, MD, PhD
role: STUDY_DIRECTOR
References: