Role of Endothelial Cells in the Pathogenesis of Chronic Urticaria.

NCT ID: NCT03443362

Last Updated: 2022-07-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

70 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-02-01

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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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

Conditions

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Chronic Urticaria

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Punch Biopsy

Intervention Type PROCEDURE

A 3 mm punch biopsy will be taken from lesional and non-lesional skin as a routine procedure.

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Control

20 healthy control patients, without chronic urticaria. Patients coming to the CHU Brugmann hospital for the excision of atypical naevi.

Punch Biopsy

Intervention Type PROCEDURE

A 3 mm punch biopsy will be taken from lesional and non-lesional skin as a routine procedure.

Blood sampling

Intervention Type PROCEDURE

Blood sampling

Interventions

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Punch Biopsy

A 3 mm punch biopsy will be taken from lesional and non-lesional skin as a routine procedure.

Intervention Type PROCEDURE

Blood sampling

Blood sampling

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Olivier Michel

OTHER

Sponsor Role lead

Responsible Party

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Olivier Michel

Head of clinic

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Yora Mostmans, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Brugmann

Locations

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CHU Brugmann

Brussels, , Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Yora Mostmans, MD

Role: CONTACT

32 2 4772272

Olivier Michel, MD

Role: CONTACT

32 2 4773664

Facility Contacts

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Yora Mostmans, MD

Role: primary

References

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Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol. 2004 Sep;114(3):465-74; quiz 475. doi: 10.1016/j.jaci.2004.02.049.

Reference Type BACKGROUND
PMID: 15356542 (View on PubMed)

Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, Church MK, Ensina LF, Gimenez-Arnau A, Godse K, Goncalo M, Grattan C, Hebert J, Hide M, Kaplan A, Kapp A, Abdul Latiff AH, Mathelier-Fusade P, Metz M, Saini SS, Sanchez-Borges M, Schmid-Grendelmeier P, Simons FE, Staubach P, Sussman G, Toubi E, Vena GA, Wedi B, Zhu XJ, Nast A, Maurer M; Dermatology Section of the European Academy of Allergy and Clinical Immunology; Golbal Allergy and Asthma European Network; European Dermatology Forum; World Allergy Organization. Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2014 Jul;69(7):e1-29. doi: 10.1111/all.12370.

Reference Type BACKGROUND
PMID: 24898678 (View on PubMed)

Greaves M. Chronic urticaria. J Allergy Clin Immunol. 2000 Apr;105(4):664-72. doi: 10.1067/mai.2000.105706.

Reference Type BACKGROUND
PMID: 10756214 (View on PubMed)

Gaig P, Olona M, Munoz Lejarazu D, Caballero MT, Dominguez FJ, Echechipia S, Garcia Abujeta JL, Gonzalo MA, Lleonart R, Martinez Cocera C, Rodriguez A, Ferrer M. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol. 2004;14(3):214-20.

Reference Type BACKGROUND
PMID: 15552715 (View on PubMed)

Hellgren L. The prevalence of urticaria in the total population. Acta Allergol. 1972;27(3):236-40. doi: 10.1111/j.1398-9995.1972.tb01420.x. No abstract available.

Reference Type BACKGROUND
PMID: 4678809 (View on PubMed)

Zuberbier T, Balke M, Worm M, Edenharter G, Maurer M. Epidemiology of urticaria: a representative cross-sectional population survey. Clin Exp Dermatol. 2010 Dec;35(8):869-73. doi: 10.1111/j.1365-2230.2010.03840.x.

Reference Type BACKGROUND
PMID: 20456386 (View on PubMed)

Sumpio BE, Riley JT, Dardik A. Cells in focus: endothelial cell. Int J Biochem Cell Biol. 2002 Dec;34(12):1508-12. doi: 10.1016/s1357-2725(02)00075-4.

Reference Type BACKGROUND
PMID: 12379270 (View on PubMed)

Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006 Jun;368(1-2):33-47. doi: 10.1016/j.cca.2005.12.030. Epub 2006 Mar 10.

Reference Type BACKGROUND
PMID: 16530177 (View on PubMed)

Coleman JW, Holliday MR, Kimber I, Zsebo KM, Galli SJ. Regulation of mouse peritoneal mast cell secretory function by stem cell factor, IL-3 or IL-4. J Immunol. 1993 Jan 15;150(2):556-62.

Reference Type BACKGROUND
PMID: 7678275 (View on PubMed)

Asero R, Tedeschi A, Lorini M, Gerosa M, Meroni P, Riboldi P. Circulating stem cell factor in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2003 Jul;91(1):79-81. doi: 10.1016/S1081-1206(10)62063-7.

Reference Type BACKGROUND
PMID: 12877454 (View on PubMed)

Kuwana M, Okazaki Y. Quantification of circulating endothelial progenitor cells in systemic sclerosis: a direct comparison of protocols. Ann Rheum Dis. 2012 Apr;71(4):617-20. doi: 10.1136/annrheumdis-2011-200713. Epub 2012 Jan 17.

Reference Type BACKGROUND
PMID: 22258488 (View on PubMed)

Yang Z, Wang JM, Chen L, Luo CF, Tang AL, Tao J. Acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects. J Hum Hypertens. 2007 Jun;21(6):452-60. doi: 10.1038/sj.jhh.1002171. Epub 2007 Mar 15.

Reference Type BACKGROUND
PMID: 17344910 (View on PubMed)

Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation. 2001 Oct 2;104(14):1694-740. doi: 10.1161/hc3901.095960. No abstract available.

Reference Type BACKGROUND
PMID: 11581152 (View on PubMed)

Cutolo M, Sulli A, Pizzorni C, Smith V. Capillaroscopy as an Outcome Measure for Clinical Trials on the Peripheral Vasculopathy in SSc-Is It Useful? Int J Rheumatol. 2010;2010:784947. doi: 10.1155/2010/784947. Epub 2010 Aug 16.

Reference Type BACKGROUND
PMID: 20827384 (View on PubMed)

Mostmans Y, De Smedt K, Feoli F, Waelput W, De Maertelaer V, Olemans C, Meiers I, Cielen T, Corazza F, Michel O, Richert B. Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study. Clin Exp Dermatol. 2024 Nov 22;49(12):1659-1667. doi: 10.1093/ced/llae252.

Reference Type DERIVED
PMID: 38963799 (View on PubMed)

Other Identifiers

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CHUB-Chronic urticaria

Identifier Type: -

Identifier Source: org_study_id

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