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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Disorders of Glycosylation
• Intervention / Treatment: Biological: Peripheral blood puncture

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Necker Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• rejection to participate in research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: CDG with stroke-like history	Biological: Peripheral blood puncture; Endothelial progenitor cells will be isolated from peripheral blood by density gradient and cultured in 10%FBS EGM2 medium On the EPCs we will study: the endothelial permeability; the protein C system
Other: CDG without stroke-like history	Biological: Peripheral blood puncture; Endothelial progenitor cells will be isolated from peripheral blood by density gradient and cultured in 10%FBS EGM2 medium On the EPCs we will study: the endothelial permeability; the protein C system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Endothelial permeability assay in basal condition	at inclusion
Endothelial permeability assay after an heat shock	at inclusion

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Pascale De Lonlay, MD, PhD, Assistance Publique - Hôpitaux de Paris; Study Director: Delphine Borgel, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2017
• Primary Completion (Actual): April 26, 2019
• Study Completion (Actual): April 26, 2019

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 11, 2017
• First Posted (Actual): August 16, 2017

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: CDG; Stroke-like; Endothelial progenitor cells (EPCs); Protein C; Congenital Disorders og Glycosylation
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital Disorders of Glycosylation
• Other Study ID Numbers: K170703J; 2017-A02141-52 (Registry Identifier: ANSM-IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No