Biomarker for Hereditary AngioEdema Disease (BioHAE)

Biomarker for Hereditary AngioEdema Disease: An International, Multicenter, Longitudinal Monitoring Protocol

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

Study Overview

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

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 Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Armenia
  • Yerevan, Armenia, 0014
    • Arabkir JMC-ICAH
• Georgia
  • Tbilisi, Georgia, 0159
    • Center of Allergy and Immunology
• India
  • Kerola, India, 682041
    • Department of Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre
• Peru
  • Lima, Peru, 1030
    • Clinica San Pablo de Surco
• Poland
  • Krakau, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie
• Romania
  • Târgu-Mureş, Romania, 547530
    • Centrul Clinic Mediquest
• Turkey
  • Sakarya, Turkey, 54100
    • Sakarya University Research and Training hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants diagnosed with Hereditary Angioedema (HAE) disease

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Participants with Hereditary Angioedema; Participants diagnosed with Hereditary Angioedema disease aged between 2 months and 60 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients	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.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the clinical robustness, specificity, and predictive value of the biomarker(s)	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.	36 months

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful Links

• CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patients

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2018
• Primary Completion (Actual): March 11, 2022
• Study Completion (Actual): March 11, 2022

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 24, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 23, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Biomarker; Hereditary Angioedema; Hereditary Angioedema Type I; Hereditary Angioedema Type II; Hereditary Angioedema Type III
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Hereditary Angioedema Type III
• Other Study ID Numbers: BHAE 06-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No