Clinical trial NCT03029728: Biomarker for Hereditary AngioEdema Disease
Official title: Biomarker for Hereditary AngioEdema Disease: An International, Multicenter, Longitudinal Monitoring Protocol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: C1 Esterase Inhibitor Deficiency
Angio Edema
C4 Deficiency
HAE
Hereditary Angioedema
Hereditary Angioedema Type II
Hereditary Angioedema Type III
Hereditary Angioedema Type I
Keywords: Hereditary Angioedema
Biomarker
Hereditary Angioedema Type I
Hereditary Angioedema Type II
Hereditary Angioedema Type III
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2017-01-24
Enrollment: 42
Sex: ALL
Minimum age (years): 2
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants diagnosed with Hereditary Angioedema (HAE) disease

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.

Eligibility criteria: INCLUSION CRITERIA

* Informed consent is obtained from the participant or participant's parent/legal guardian
* The participant is aged between 2 months and 60 years
* The diagnosis of Hereditary Angioedema is confirmed by CENTOGENE

EXCLUSION CRITERIA

* Inability to provide informed consent
* Participant is younger than 2 months or older than 60 years
* The diagnosis of Hereditary Angioedema disease is not confirmed by CENTOGENE

Primary outcomes:
measure: Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients
timeFrame: 36 months
Secondary outcomes:
measure: Determination of the clinical robustness, specificity, and predictive value of the biomarker(s)
timeFrame: 36 months
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Arabkir JMC-ICAH
city: Tbilisi
country: Georgia
facility: Center of Allergy and Immunology
city: Kerola
country: India
facility: Department of Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre
city: Lima
country: Peru
facility: Clinica San Pablo de Surco
city: Krakau
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Târgu-Mureş
country: Romania
facility: Centrul Clinic Mediquest
city: Sakarya
country: Turkey
facility: Sakarya University Research and Training Hospital
Study officials:
affiliation: CENTOGENE GmbH
name: Peter Bauer, MD
role: STUDY_CHAIR
References: