Clinical trial NCT02671006: Monitoring Chronic Urticaria Basophil Irritability by Cytometry
Official title: Monitoring Chronic Urticaria Basophil Irritability by Cytometry (Monocentric Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urticaria
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2016-02-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient analysis will be performed on

* 30 patients with an active CU according to the EAACI criteria.
* 30 volunteers with no history of immediate allergy (patients under medical follow up for melanoma in remission for at least 3 months, age (+/- 5 years) and sex matched). Controls should have no history of atopy, urticaria or immediate allergy declared (rhinitis, urticaria, asthma) at the time of the test. Blood sample will be collected during a venipuncture required for the medical follow up and should not interfere with the usual treatment.

Brief summary: A biological tool for quantitative assessment of Chronic Urticaria (CU) is still in need for monitoring biotherapies. CU is considered as a sudden degranulation of Mast cells / basophils without any identified cause. It is considered that Mast cell/basophil have an abnormally high sensitivity in CU and can be triggered with almost nothing (high irritability). In allergy, basophils degranulation can be reproduced in vitro with allergens. Anti-IgE (immunoglobulin E) antibody mimics allergen triggering of basophils in a dose dependent manner. If basophils are abnormally sensitive in CU, it should be reproduced in vitro at very low stimulation. The main objective of this project is to set up a method to evidence abnormal basophil irritability and look for clinical significance. As many markers characterize basophils in different states, researchers shall also look for a profile possibly associated with CU basophile irritability. Such tests could be useful in CU monitoring.

Detailed description: Mast cell is a key factor in Urticaria physiopathology. Several mechanisms have been hypothesized and could be either synergistic or revealing different types of urticaria. But most of these mechanisms seem to converge to Mast cells releasing histamine and other products. These mechanisms include auto-antibody and / or cytokines inappropriate production. However, internal dysregulation of Mast cell have also been reported, that could be either primary or secondary to extrinsic mediators mentioned already. Basophils closely related to Mast cells, easily accessible and usually serve as surrogate for clinical analysis of allergy or urticaria.

Flow-cytometry (FCM) is a recent tool with increasing interest due to its exceptional capacity of analysis of a large number of cells, individually, at high speed and measuring many parameters at a time. FCM has been extensively used in characterization of cell sub populations in several diseases such as hematology disorders or immunology and among them the basophil. FCM is now the gold standard for ex vivo functional analyses of basophil activation as part of the diagnosis of allergy.

The present project aims to explore phenotypic and functional changes that could reflect the dysregulation in Urticaria. This would have diagnosis and physiopathological interest with potential impact on optimizing disease monitoring and treatment.

Eligibility criteria: Inclusion Criteria:

* Patients :
* Active Chronic Urticaria according to the EAACI 2014 criteria.
* Healthy volunteers :
* Age (approx. +/- 5 years matched with patient group),
* Sexe matched.

Exclusion Criteria:

* Patients
* Treated by Omalizumab
* Healthy volunteers :
* Allergy,
* Atopy,
* Urticaria.

Primary outcomes:
measure: Critical dose of anti IgE triggering half of basophils
timeFrame: Day 1
Secondary outcomes:
measure: Antigen Density
timeFrame: Day 1
measure: Urticaria Control Tests (UCT)
timeFrame: Day 1
measure: Urticaria Activity Score 7 (UAS7)
timeFrame: Day 1
measure: Optical Coherence Tomography (OCT)
timeFrame: Day 1
measure: D Dimers dosage
timeFrame: Day 1
measure: IL33 dosage
timeFrame: Day 1
measure: Tryptase
timeFrame: Day 1
Other outcomes:
Locations:
city: Saint Etienne
country: France
facility: Chu Saint Etienne
Study officials:
affiliation: CHU SAINT-ETIENNE
name: LAMBERT Claude, MD
role: PRINCIPAL_INVESTIGATOR
References: