C1 Esterase Inhibitor DeficiencyBioHAENCT03029728
Biomarker for Hereditary AngioEdema Disease
An observational study of C1 Esterase Inhibitor Deficiency and Angio Edema, run by CENTOGENE GmbH Rostock at 7 sites in 7 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 2 months to 60 years
- Conditions the study is for
- C1 Esterase Inhibitor Deficiency, Angio Edema, C4 Deficiency
- How many people
- 42 participants
- Where
- 7 sitesin 7 countries
- Study dates
- 20 Aug 2018to 11 Mar 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Participants diagnosed with Hereditary Angioedema (HAE) disease
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 7 countries.
7 sites in 7 countries
India1 site
Department of Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre
Kerola, 682041
Turkey (Türkiye)1 site
Sakarya University Research and Training Hospital
Sakarya, 54100
About this study
Official title: 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
Read the 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.
- Conditions
- C1 Esterase Inhibitor Deficiency, Angio Edema, C4 Deficiency, HAE, Hereditary Angioedema, Hereditary Angioedema Type II
- Keywords
- Hereditary Angioedema, Biomarker, Hereditary Angioedema Type I, Hereditary Angioedema Type II, Hereditary Angioedema Type III
- Medical subject headings
- Angioedemas, Hereditary, Angioedema, Hereditary Angioedema Types I and II, Hereditary Angioedema Type III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Participants with Hereditary Angioedema | Participants diagnosed with Hereditary Angioedema disease aged between 2 months and 60 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 36 months
Secondary outcomes (1)
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.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start20 Aug 2018
- Primary completion11 Mar 2022
- Study completion11 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for C1 Esterase Inhibitor DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- CENTOGENE GmbH Rostock
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Bauer, MD, Study chair, CENTOGENE GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029728
- Sponsor's protocol ID
- BHAE 06-2018
- Acronym
- BioHAE
- Status last verified
- Mar 2021
- First submitted
- 18 Jan 2017
- Last updated
- 24 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker for Hereditary AngioEdema Disease: An International, Multicenter, Longitudinal Monitoring Protocol
- ClinicalTrials.gov ID
- NCT03029728
- Acronym / sponsor ID
- BioHAE / BHAE 06-2018
- Conditions
- C1 Esterase Inhibitor Deficiency, Angio Edema, C4 Deficiency, HAE, Hereditary Angioedema, Hereditary Angioedema Type II
- Keywords
- Hereditary Angioedema, Biomarker, Hereditary Angioedema Type I, Hereditary Angioedema Type II, Hereditary Angioedema Type III
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- CENTOGENE GmbH RostockIndustry (pharma, biotech, devices)
- Study start
- 20 Aug 2018 (actual)
- Primary completion
- 11 Mar 2022 (actual)
- Study completion
- 11 Mar 2022 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Hereditary Angioedema | – | –Participants diagnosed with Hereditary Angioedema disease aged between 2 months and 60 years |
Who may qualify
- Ages
- 2 months to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Participants diagnosed with Hereditary Angioedema (HAE) disease
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients
Time frame: 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.
1 secondary outcome
Determination of the clinical robustness, specificity, and predictive value of the biomarker(s)
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
- CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patientsLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Bauer, MD study chair
CENTOGENE GmbH
7 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of C1 Esterase Inhibitor Deficiency and Angio Edema, run by CENTOGENE GmbH Rostock at 7 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Armenia, Georgia, India, Peru, Poland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2022.