Evaluation of New Markers in Type 3 Angioedema

• Sponsor: Brugmann University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03917680
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 6
• Actual Duration (Months): 11.3
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Angio Edema	Diagnostic Test: Factor XII dosage; Genetic: p.Thr328Lys mutation detection; Diagnostic Test: Videocapillaroscopy	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of New Markers (FXII and Videocapillaroscopy) in Type 3 Angioedema
• Actual Study Start Date: Oct 29, 2018
• Actual Primary Completion Date: Oct 8, 2019
• Actual Study Completion Date: Oct 8, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Plasma concentration of Factor XII [24 hours]

   Plasma concentration of Factor XII

2. Presence of p.Thr328Lys mutation [24 hours]

   Genetic analysis : sequencing of the Factor VII gene. Presence/Absence of the p.Thr328Lys mutation (single nucleotide variation inducing a missense variant).

3. Videocapillaroscopy result [24 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

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

Exclusion Criteria:

• None

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU Brugmann	Brussel		Belgium	1020

Sponsors and Collaborators

• Brugmann University Hospital

Investigators

• Principal Investigator: Oumnia Mouna, MD, CHU Brugmann

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Olivier Michel, Head of immuno-allergology clinic, Brugmann University Hospital
• ClinicalTrials.gov Identifier: NCT03917680
• Other Study ID Numbers: CHUB-angiodema
• First Posted: Apr 17, 2019
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Angioedema

Study Results

No Results Posted as of Jan 18, 2020