Evaluation of New Markers in Type 3 Angioedema

Evaluation of New Markers (FXII and Videocapillaroscopy) in Type 3 Angioedema

Angioedema is a common condition, with multiple etiologies.

Type 3 angioedema is caused by an increase in kininogenase activity responsible for an increased production of bradykinin. In some cases, it may be associated with clotting factor 12 mutations. However, other genetic abnormalities remain to be identified.

Clinically, this angioedema type 3 is similar to types 1 and 2. The patient's vital prognosis is good if the diagnosis is made and if they have access to the appropriate treatment. Otherwise a significant morbidity is associated with it, hence the importance of being able to define a diagnostic marker.

Videocapillaroscopy might be able to highlight abnormalities in the microcirculation of patients with a clinical display of angioedema.

The purpose of this study is to highlight markers allowing to make an early diagnosis of angioedema. Functional analysis of factor XII in patients with symptoms of angioedema may be an interesting marker for diagnosis.

Microcirculation abnormalities will also be evaluated by videocapillaroscopy, which may be another indicator of the disease.

Study Overview

• Status: Completed
• Conditions: Angio Edema
• Intervention / Treatment: Diagnostic test: Factor XII dosage; Genetic: p.Thr328Lys mutation detection; Diagnostic test: Videocapillaroscopy

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1020
    • CHU Brugmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Population of patients treated within the CHU Brugmann Hospital for an angioedema (and control group of healthy individuals)

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Type III angioedema; White angioedema. Positive for Factor XII mutation. No C1-inhibitors anomaly. Not caused by IEC.	Diagnostic test: Factor XII dosage; Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.; Genetic: p.Thr328Lys mutation detection; Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.; Diagnostic test: Videocapillaroscopy; It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.
Experimental: Idiopathic angioedema; White angioedema. Negative for Factor XII mutation. No C1-inhibitors anomaly. Not caused by IEC.	Diagnostic test: Factor XII dosage; Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.; Genetic: p.Thr328Lys mutation detection; Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.; Diagnostic test: Videocapillaroscopy; It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.
Experimental: Type I or II angioedema; White angioedema. Negative for Factor XII mutation. C1-inhibitors anomaly. Not caused by IEC.	Diagnostic test: Factor XII dosage; Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.; Genetic: p.Thr328Lys mutation detection; Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.; Diagnostic test: Videocapillaroscopy; It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.
Experimental: Post IEC (conversion enzyme inhibitors) angioedema; White angioedema. Negative for Factor XII mutation. No C1-inhibitors anomaly. Caused by IEC.	Diagnostic test: Factor XII dosage; Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.; Genetic: p.Thr328Lys mutation detection; Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.; Diagnostic test: Videocapillaroscopy; It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.
Experimental: Histaminic angioedema; Red angioedema.Negative for Factor XII mutation. No C1-inhibitors anomaly. Not caused by IEC.	Diagnostic test: Factor XII dosage; Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.; Genetic: p.Thr328Lys mutation detection; Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.; Diagnostic test: Videocapillaroscopy; It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.
Other: Control; Healthy individuals, no angioedema.	Diagnostic test: Videocapillaroscopy; It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of Factor XII	Plasma concentration of Factor XII	24 hours
Presence of p.Thr328Lys mutation	Genetic analysis : sequencing of the Factor VII gene. Presence/Absence of the p.Thr328Lys mutation (single nucleotide variation inducing a missense variant).	24 hours
Videocapillaroscopy result	It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.The result will be classified as 'normal' or 'abnormal' by the videocapillaroscopy specialist.	24 hours

Collaborators and Investigators

• Sponsor: Brugmann University Hospital
• Investigators: Principal Investigator: Oumnia Mouna, MD, CHU Brugmann

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2018
• Primary Completion (Actual): October 8, 2019
• Study Completion (Actual): October 8, 2019

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 15, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Angioedema
• Other Study ID Numbers: CHUB-angiodema

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