Biomarker for Hereditary AngioEdema Disease

Completed

• Conditions: C4 Deficiency; Hereditary Angioedema Type I; C1 Esterase Inhibitor Deficiency; HAE; Hereditary Angioedema Type II; Angio Edema; Hereditary Angioedema; Hereditary Angioedema Type III

• Registration Number: NCT03029728
• Lead Sponsor: CENTOGENE GmbH Rostock

Brief Summary

International, multicenter, observational, longitudinal monitoring study to identify, validate and/or monitor Mass Spectrometry (MS)-based biomarker/s for Hereditary Angioedeme (HAE) disease and to test the clinical robustness, specificity, and predictive value of theese biomarker/s

Detailed Description

Hereditary Angioedema (HAE) is a rare autosomal dominant genetic disorder, characterized by recurrent episodes of angioedema of the face, larynx, lips, abdomen, and extremities.The most common types of HAE develop as result of mutations in the SERPING1 gene that encodes the C1 inhibitor (C1-INH), a protease involved in limiting bradykinin production. Excessive bradykinin due to low levels of C1-INH (HAE type 1) or dysfunctional C1-INH (HAE type 2) leads to capillary leakage and angioedema formation. The third type of HAE is not associated with a C1-INH deficiency, develops as a result of mutations in the Factor 12 gene (FXII) and affects almost exclusively women. Rare cases of HAE have also been described resulting from mutations in Plasminogen (PLG), Angiopoetin 1 (ANGPT1), and Kininogen 1 (KNG1).

The characteristic symptom of hereditary angioedema is recurrent episodes of swelling due to the accumulation of excessive body fluid. The most commonly affected areas of the body include the hands, feet, eyelids, lips, genitals, larynx and gastrointestinal tract. The most serious complication of HAE is laryngeal edema that can become life threatening; but it is a relatively rare event.

The diagnosis of hereditary angioedema is made by a thorough clinical evaluation, a detailed patient history, and blood tests.Clinical diagnosis is complicated because HAE is highly variable in the clinical phenotype and the majority of the physicians believe that they never seen a patient with that disorder. Laboratory diagnosis involves measurement of the C1-INH function, C1-INH and C4 levels. Both C1-INH protein level and function is low in HAE-1 patients, whereas in HAE-2 individuals the C1-INH concentrations is optimal or even elevated, however C1-INH function is impaired. Generally, C4 levels are low in both HAE-1/2 patients.

CENTOGENE utilizes Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry (LC-MRM-MS) method to identify potential disease-specific biomarkers for HAE. Such biomarker/s may support the early diagnosis and treatment monitoring and personalization in the future.

Therefore, it is the goal of this study is to identify new biomarkers for HAE, validate the identified biomarkers, and monitor these biomarkers longitudinally to determine their clinical robustness, specificity, and predictive value.

Study Timeline

• Study First Submitted: 2017-01-18
• Study First Submitted QC: 2017-01-23
• Study First Posted: 2017-01-24
• Study Start: 2018-08-20
• Status Verified: 2021-03
• Primary Completion: 2022-03-11
• Study Completion: 2022-03-11
• Last Update Submitted: 2022-03-23
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients	36 months	All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

Secondary Outcome Measures

Name	Time	Method
Determination of the clinical robustness, specificity, and predictive value of the biomarker(s)	36 months	Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

Trial Locations

Locations (7)

Center of Allergy and Immunology; 🇬🇪 Tbilisi, Georgia

Department of Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre; 🇮🇳 Kerola, India

Clinica San Pablo de Surco; 🇵🇪 Lima, Peru

Centrul Clinic Mediquest; 🇷🇴 Târgu-Mureş, Romania

Sakarya University Research and Training Hospital; 🇹🇷 Sakarya, Turkey

Arabkir JMC-ICAH; 🇦🇲 Yerevan, Armenia

Szpital Uniwersytecki w Krakowie; 🇵🇱 Krakau, Poland