Role of Endothelial Cells in the Pathogenesis of Chronic Urticaria.

July 18, 2022 updated by: Olivier Michel

Prospective, Observational, Longitudinal Cohort Study on the Role of Endothelial Cells in the Pathogenesis of Chronic Urticaria.

Chronic urticaria (CU) is a disease that usually affects a large visible amount of surface of the skin. It is accompanied by severe itch and feeling of burned skin. Therefore the disease has a big impact on the quality of life of patients. Unfortunately, to date CU is not easily controlled by its few existing treatment options (i.e. antihistamines, omalizumab, cyclosporine).

This research's main perspective is to improve quality of life for CU patients by first of all focusing on a good clinical diagnosis of (different subtypes of) CU in a CU reference center, and secondly by gaining more insight on the pathogenesis of the disease to expand knowledge on potential new targeted treatments for the patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chronic urticaria (CU) is an inflammatory skin disease that is defined by the presence of urticaria (hives), on most days of the week, for a period of six weeks or longer. About 40 percent of patients with CU have accompanying episodes of angioedema. It is classified as chronic inducible urticaria (CIU) in which urticaria is induced by one or more environmental stimuli (such as heat, cold, pressure applied to the skin, exercise, water, vibration, and sunlight) and chronic spontaneous urticaria (CSU) which refers to CU in which appearance of lesions is not triggered by consistent or identifiable factors. At any given time, CU affects up to 1 percent of the general population in the United States, and the prevalence is believed to be similar in other countries. So far, epidemiological studies for a Belgian population haven't been performed yet.

It is generally proposed that patients with CU have defects in mast cell and/or basophil trafficking, signaling and/or function. Nevertheless more recently also other cells seem to be involved: lymphocytes, eosinophils, endothelial cells (ECs). The integrity of EC structure and function is important in the maintenance of the vessel wall and circulatory function. As a barrier, the endothelium is semi-permeable and controls molecular transport between the blood and the tissues. Under basal conditions, ECs are involved in maintaining the anti-thrombotic blood-tissue interface by regulating thrombosis, thrombolysis, platelet adherence, vascular tone and blood flow. In CU, mast cells are activated and histamine release occurs. This histamine binds to its receptor on the ECs causing vasodilation and extravasation. This endothelial function/dysfunction can be characterized by several biological markers from different signalization/activation pathways. Vascular injury induces release of vascular endothelial growth factor (VEGF) to stimulate angiogenesis. Cytokine stimulation triggers the expression and release of adhesion molecules (e.g., E-selectin, ICAM-1, VCAM-1), making transendothelial migration of lymphocytes possible. In particular, E-selectin is expressed only by activated endothelium; however, its circulating form (sE-selectin) can be found in the plasma after enzymatic cleavage or from shedding by damaged or active ECs. Furthermore it is known for ECs to interact with mast cells through the production of Stem Cell Factor (SCF; c-kit ligand) to influence mast cell proliferation and differentiation. Asero et al (2003) determined serum SCF levels in 65 CIU patients and found no difference from those found in healthy controls. Nevertheless, the increase in mast cells in skin biopsy specimens, along with the absence of systemic eosinophilia in CIU patients suggests a possible role for stem cell factor (SCF) in CU pathogenesis.

Endothelial progenitor cells (EPC) normally have the ability to develop into fully mature EC and contribute to neovascularization by targeting sites of endothelial injury. Furthermore it is shown that acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects. Since exercise is a known trigger for CU, it would be interesting to investigate the effect of exercise on EPC recruitment and EC activation in CSU.

Microvascular damage and EC injury is described in multiple diseases such as diabetes and scleroderma. This can be evaluated by nail fold videocapillaroscopy (NVC). The integrity of vessel walls is compromised in CU, of which the appearance of wheals due to the extravasation process seems to be the most obvious symptom clinically. It would be interesting to examine if there are microscopical abnormalities on NVC that could help identify (certain subtypes of) CU. If present, correlations between these abnormalities and disease severity can be further investigated.

The objectives of the study are:

  • To determine the incidence of CU (CSU and CIU) in a Belgian city center hospital
  • To investigate the role of ECs in CSU on a clinical and molecular level

Study Type

Observational

Enrollment (Anticipated)

70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Brussel, Belgium, 1020
        • Recruiting
        • CHU Brugmann
        • Contact:
          • Yora Mostmans, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients with a diagnose of chronic urticaria receiving medical care within the CHU Brugmann Hospital. Diagnose performed according to the European Academy of Allergy and Clinical Immunology (EAACI) guidelines.

The control group consists in patients beeing followed within the CHU Brugmann Hospital for the ellipsoid excision of atypical naevi on remnant healthy skin.

Description

Inclusion Criteria:

All patients diagnosed with chronic urticaria receiving medical care within the CHU Brugmann Hospital. Diagnose performed according to the European Academy of Allergy and Clinical Immunology (EAACI) guidelines.

Exclusion Criteria:

None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Chronic urticaria
50 consecutive chronic urticaria patients receiving medical care within the CHU Brugmann Hospital. Diagnose according to the European Academy of Allergy and Clinical Immunology (EAACI) guidelines.
Procedure: Blood sampling
Blood sampling
Procedure: Punch Biopsy
A 3 mm punch biopsy will be taken from lesional and non-lesional skin as a routine procedure.
Control
20 healthy control patients, without chronic urticaria. Patients coming to the CHU Brugmann hospital for the excision of atypical naevi.
Procedure: Blood sampling
Blood sampling
Procedure: Punch Biopsy
A 3 mm punch biopsy will be taken from lesional and non-lesional skin as a routine procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stem cell factor expression
Time Frame: 6 months
Immunohistochemistry performed on cryostat sections with a monoclonal antibody
6 months
E-selectin expression
Time Frame: 6 months
Immunohistochemistry performed on paraformaldehyde fixed sections with a monoclonal antibody
6 months
Vascular endothelial growth factor (VEGF) expression
Time Frame: 6 months
Immunohistochemistry performed with a monoclonal antibody on paraffin sections
6 months
C5B9 complement complex expression
Time Frame: 6 months
Immunofluorescence staining performed on paraffin-embedded tissue blocks
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of chronic inducible urticaria
Time Frame: 6 months
Incidence of chronic inducible urticaria within the CHU Brugmann Hospital. Diagnose established by means of provocation tests.
6 months
Incidence of chronic spontaneous urticaria
Time Frame: 6 months
Incidence of chronic spontaneous urticaria within the CHU Brugmann Hospital. Diagnose established by means of provocation tests.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Olivier Michel

Investigators

  • Principal Investigator: Yora Mostmans, MD, CHU Brugmann

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 1, 2018

Primary Completion (ANTICIPATED)

December 1, 2022

Study Completion (ANTICIPATED)

December 1, 2022

Study Registration Dates

First Submitted

February 16, 2018

First Submitted That Met QC Criteria

February 16, 2018

First Posted (ACTUAL)

February 23, 2018

Study Record Updates

Last Update Posted (ACTUAL)

July 19, 2022

Last Update Submitted That Met QC Criteria

July 18, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUB-Chronic urticaria

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Urticaria

Clinical Trials on Blood sampling

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in India

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe