Hereditary AngioedemaBRADYKIDNCT02854397
Determination of Specific Biomarkers of Acute Attack of Angioedema Within Pediatric Population
An observational study of Hereditary Angioedema and Healthy Volunteers, run by University Hospital, Grenoble at 14 sites in France.
Trial summary
In emergency room, this is crucial to diagnose an acute attack of hereditary angioedema (HAE) to quickly provide the efficient treatment. Currently, there is no specific biomarker for acute attack of bradykinin-mediated angioedema to help clinicians for patient care. Read more about this study
- Who is it for?
- Ages 1 year to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Angioedema, Healthy Volunteers
- What is being tested?
- blood sample
- How many people
- 31 participants
- Where
- 14 sitesFrance
- Study dates
- 15 Feb 2016to Jun 2020
- 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 1 year to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: patients with hereditary angioedema patients with angioedema resulting of mast cell activation healthy patients, without angioedema
Who may be able to join
- For HAE: patient with a documented diagnosis of HAE:
- type I (from an antigenic deficiency of the C1 esterase inhibitor) or type II (from a functional deficiency of the C1 esterase inhibitor). The existence of a mutation in SERPING1 was not necessary for the inclusion
- HAE with normal C1-INH (ex type III) with a required mutation in FXII gene or with a typical family history of HAE diagnosed by a specialized physician belonging to CREAK network.
- For AE resulting of mast cell activation: a documented diagnosis of AE resulting of mast cell activation included:
- mastocytosis,
- chronic spontaneous urticaria,
Show all 10Show fewer
- acute urticaria after exposure of allergen during allergy challenge tests,
- mast cell activation syndrome.
- For the control group:
- composed of patients who presented a stabilized disease (that was not infectious, not auto-inflammatory or inflammatory disease and without implication of endothelial cells).
Who cannot join
- Over 18 years or under 1 year.
- Diagnosis of HAE with a normal C1 esterase inhibitor or AE of unknown aetiology.
- Patients with HAE who received an acute attack treatment before the blood sample (the C1 esterase inhibitor concentrate or a bradykinin B2 receptor antagonist); patients with HAE who received a prophylactic treatment (danazol).
- Patients who were treated by omalizumab or corticosteroid treatment.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
France14 sites
University hospital angers
Angers, 49933
University Hospital Besançon
Besançon, 25030
University hospital Bordeaux
Bordeaux, 33076
University hopital Clermont-Ferrand
Clermont-Ferrand, 63503
University Hospital Grenoble
Grenoble, 38043
University Hospital Lille
Lille, 59037
University Hospital Lyon
Lyon, 69677
University hospital Marseille
Marseille, 13385
University hospital Montpellier
Montpellier, 34295
University hospital Nancy
Nancy, 54500
General Hospital
Niort, 79021
university hospital Saint-Antoine (AP-HP)
Paris, 75571
University hospital Rouen
Rouen, 76031
University hospital Toulouse
Toulouse, 31059
About this study
In emergency room, this is crucial to diagnose an acute attack of hereditary angioedema (HAE) to quickly provide the efficient treatment. Currently, there is no specific biomarker for acute attack of bradykinin-mediated angioedema to help clinicians for patient care. However, previous works are carried out for that purpose. All the potential candidate biomarkers must be validated in prospective studies to estimate their specificity and sensitivity values, and to understand their potential utility in patient care.
The main goal of this clinical trial is to estimate the diagnostic value of VE-cadherin in pediatric population, for the differential diagnosis between HAE crisis and angioedema resulting of mast cell activation crisis (the main differential diagnosis of HAE).
- Conditions
- Hereditary Angioedema, Healthy Volunteers
- Being tested
- blood sample
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleOther
| Study group | Role | What they receive |
|---|---|---|
| patients with hereditary angioedema | A blood sample will be performed in crisis and 7 days after the crisis. Receives: Other: blood sample | |
| patients with angioedema resulting of mast cell activation | A blood sample will be performed in crisis and 7 days after the crisis. Receives: Other: blood sample | |
| healthy patients, without angioedema | A quantity of additional blood was taken from eligible patients who had a scheduled blood sample. Receives: Other: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
VE-cadherin level
For the diagnosis of acute attack of hereditary angioedema
Measured: Half a day
Secondary outcomes (4)
Dosage of VE-cadherin (vascular endothelial)
Analysis of the cleaved fragments from high molecular weight kininogen
Measured: Half a day
Dosage of Fc KHPM
Analysis of the cleaved fragments from high molecular weight kininogen
Measured: Half a day
Dosage of D-dimer
Analysis of the cleaved fragments from high molecular weight kininogen
Measured: Half a day
Dosage of Tryptase
Analysis of the cleaved fragments from high molecular weight kininogen
Measured: Half a day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2016 (estimated)
- Study start15 Feb 2016
- Primary completionJun 2020
- Study completionJun 2020
Why it stopped: Recruitment difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- 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
- Other
- Time perspective
- Prospective
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne Pagnier, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02854397
- Sponsor's protocol ID
- 38RC15.180
- Acronym
- BRADYKID
- Status last verified
- Nov 2020
- First submitted
- 18 Jul 2016
- Last updated
- 18 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Boccon-Gibod I, Bouillet L. [Angioedema and urticaria]. Ann Dermatol Venereol. 2014 Nov;141 Suppl 3:S586-95. doi: 10.1016/S0151-9638(14)70162-0. French.
PubMed 25539680Pagnier A. [Hereditary angioedema in childhood. Diagnosis and therapeutic challenges]. Presse Med. 2015 Jan;44(1):89-95. doi: 10.1016/j.lpm.2014.07.018. Epub 2014 Dec 12. French.
PubMed 25511651Dinkel HP, Maroske J, Schrod L. Sonographic appearances of the abdominal manifestations of hereditary angioedema. Pediatr Radiol. 2001 Apr;31(4):296-8. doi: 10.1007/s002470000409.
PubMed 11321752Bygum A. Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009 Nov;161(5):1153-8. doi: 10.1111/j.1365-2133.2009.09366.x. Epub 2009 Jun 22.
PubMed 19709101Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):18. doi: 10.1186/1710-1492-6-18.
PubMed 20667121El-Hachem C, Amiour M, Guillot M, Laurent J. [Hereditary angioneurotic edema: a case report in a 3-year-old child]. Arch Pediatr. 2005 Aug;12(8):1232-6. doi: 10.1016/j.arcped.2005.03.052. French.
PubMed 15890504Farkas H. Management of upper airway edema caused by hereditary angioedema. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):19. doi: 10.1186/1710-1492-6-19.
PubMed 20667122Sanchez A, Ecochard A, Maestracci M, Rodiere M. [Hereditary angioedema causing colocolic intussusception]. Arch Pediatr. 2008 Mar;15(3):271-4. doi: 10.1016/j.arcped.2007.12.004. Epub 2008 Mar 10. French.
PubMed 18329867Pritzker HA, Levin TL, Weinberg G. Recurrent colocolic intussusception in a child with hereditary angioneurotic edema: reduction by air enema. J Pediatr Surg. 2004 Jul;39(7):1144-6. doi: 10.1016/j.jpedsurg.2004.03.075.
PubMed 15213920Parisi G, Chiarelli A, Squadrone NP, Galante E. Hereditary angioedema, a rare cause of recurrent abdominal pain. A report of 2 clinical cases and comments of a general nature Allergy Asthma Proc. 2013 Jul-Aug;34(4):312-27
MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol. 2014 Aug;25(5):420-7. doi: 10.1111/pai.12168. Epub 2013 Dec 9.
PubMed 24313851Deroux A, Vilgrain I, Dumestre-Perard C, Boccon-Gibod I, Bouillet L. Towards a specific marker for acute bradykinin-mediated angioedema attacks: a literature review. Eur J Dermatol. 2015 Jul-Aug;25(4):290-5. doi: 10.1684/ejd.2015.2547.
PubMed 25905454Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M. Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Allergy. 2009 Feb;64(2):254-7. doi: 10.1111/j.1398-9995.2008.01859.x. Epub 2008 Dec 4.
PubMed 19076541Hogan AD, Schwartz LB. Markers of mast cell degranulation. Methods. 1997 Sep;13(1):43-52. doi: 10.1006/meth.1997.0494.
PubMed 9281467Brickman CM, Frank MM, Kaliner M. Urine-histamine levels in patients with hereditary angioedema (HAE). J Allergy Clin Immunol. 1988 Sep;82(3 Pt 1):403-6. doi: 10.1016/0091-6749(88)90012-7.
PubMed 3170987
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Specific Biomarkers of Acute Attack of Angioedema Within Pediatric Population
- ClinicalTrials.gov ID
- NCT02854397
- Acronym / sponsor ID
- BRADYKID / 38RC15.180
- Conditions
- Hereditary Angioedema, Healthy Volunteers
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Recruitment difficulties
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 15 Feb 2016 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 3 Aug 2016 (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.
In emergency room, this is crucial to diagnose an acute attack of hereditary angioedema (HAE) to quickly provide the efficient treatment. Currently, there is no specific biomarker for acute attack of bradykinin-mediated angioedema to help clinicians for patient care. However, previous works are carried out for that purpose. All the potential candidate biomarkers must be validated in prospective studies to estimate their specificity and sensitivity values, and to understand their potential utility in patient care.
The main goal of this clinical trial is to estimate the diagnostic value of VE-cadherin in pediatric population, for the differential diagnosis between HAE crisis and angioedema resulting of mast cell activation crisis (the main differential diagnosis of HAE).
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| patients with hereditary angioedema | – | Other: blood sampleA blood sample will be performed in crisis and 7 days after the crisis. |
| patients with angioedema resulting of mast cell activation | – | Other: blood sampleA blood sample will be performed in crisis and 7 days after the crisis. |
| healthy patients, without angioedema | – | Other: blood sampleA quantity of additional blood was taken from eligible patients who had a scheduled blood sample. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- patients with hereditary angioedema patients with angioedema resulting of mast cell activation healthy patients, without angioedema
Key inclusion criteria (10 listed)
- type I (from an antigenic deficiency of the C1 esterase inhibitor) or type II (from a functional deficiency of the C1 esterase inhibitor). The existence of a mutation in SERPING1 was not necessary for the inclusion
- HAE with normal C1-INH (ex type III) with a required mutation in FXII gene or with a typical family history of HAE diagnosed by a specialized physician belonging to CREAK network.
- For AE resulting of mast cell activation: a documented diagnosis of AE resulting of mast cell activation included:
- mastocytosis,
- chronic spontaneous urticaria,
Key exclusion criteria (4 listed)
- Over 18 years or under 1 year.
- Diagnosis of HAE with a normal C1 esterase inhibitor or AE of unknown aetiology.
- Patients with HAE who received an acute attack treatment before the blood sample (the C1 esterase inhibitor concentrate or a bradykinin B2 receptor antagonist); patients with HAE who received a prophylactic treatment (danazol).
- Patients who were treated by omalizumab or corticosteroid treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sample | Other | healthy patients, without angioedema, patients with angioedema resulting of mast cell activation, patients with hereditary angioedema |
Primary outcome
VE-cadherin level
Time frame: Half a day
For the diagnosis of acute attack of hereditary angioedema
4 secondary outcomes
Dosage of VE-cadherin (vascular endothelial)
Time frame: Half a day
Dosage of Fc KHPM
Time frame: Half a day
Dosage of D-dimer
Time frame: Half a day
Dosage of Tryptase
Time frame: Half a day
Results and safety
The study was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2020.
- Background: PubMed 25539680Boccon-Gibod I, Bouillet L. [Angioedema and urticaria]. Ann Dermatol Venereol. 2014 Nov;141 Suppl 3:S586-95. doi: 10.1016/S0151-9638(14)70162-0. French.
- Background: PubMed 25511651Pagnier A. [Hereditary angioedema in childhood. Diagnosis and therapeutic challenges]. Presse Med. 2015 Jan;44(1):89-95. doi: 10.1016/j.lpm.2014.07.018. Epub 2014 Dec 12. French.
- Background: PubMed 11321752Dinkel HP, Maroske J, Schrod L. Sonographic appearances of the abdominal manifestations of hereditary angioedema. Pediatr Radiol. 2001 Apr;31(4):296-8. doi: 10.1007/s002470000409.
- Background: PubMed 19709101Bygum A. Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009 Nov;161(5):1153-8. doi: 10.1111/j.1365-2133.2009.09366.x. Epub 2009 Jun 22.
- Background: PubMed 20667121Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):18. doi: 10.1186/1710-1492-6-18.
- Background: PubMed 15890504El-Hachem C, Amiour M, Guillot M, Laurent J. [Hereditary angioneurotic edema: a case report in a 3-year-old child]. Arch Pediatr. 2005 Aug;12(8):1232-6. doi: 10.1016/j.arcped.2005.03.052. French.
- Background: PubMed 20667122Farkas H. Management of upper airway edema caused by hereditary angioedema. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):19. doi: 10.1186/1710-1492-6-19.
- Background: PubMed 18329867Sanchez A, Ecochard A, Maestracci M, Rodiere M. [Hereditary angioedema causing colocolic intussusception]. Arch Pediatr. 2008 Mar;15(3):271-4. doi: 10.1016/j.arcped.2007.12.004. Epub 2008 Mar 10. French.
- Background: PubMed 15213920Pritzker HA, Levin TL, Weinberg G. Recurrent colocolic intussusception in a child with hereditary angioneurotic edema: reduction by air enema. J Pediatr Surg. 2004 Jul;39(7):1144-6. doi: 10.1016/j.jpedsurg.2004.03.075.
- BackgroundParisi G, Chiarelli A, Squadrone NP, Galante E. Hereditary angioedema, a rare cause of recurrent abdominal pain. A report of 2 clinical cases and comments of a general nature Allergy Asthma Proc. 2013 Jul-Aug;34(4):312-27
- Background: PubMed 24313851MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol. 2014 Aug;25(5):420-7. doi: 10.1111/pai.12168. Epub 2013 Dec 9.
- Background: PubMed 25905454Deroux A, Vilgrain I, Dumestre-Perard C, Boccon-Gibod I, Bouillet L. Towards a specific marker for acute bradykinin-mediated angioedema attacks: a literature review. Eur J Dermatol. 2015 Jul-Aug;25(4):290-5. doi: 10.1684/ejd.2015.2547.
- 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.
Anne Pagnier principal investigator
University Hospital, Grenoble
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Angioedema and Healthy Volunteers, run by University Hospital, Grenoble at 14 sites in France.
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 10 inclusion and 4 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: stopped early, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France. 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 was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
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?
VE-cadherin level (time frame: Half a day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02854397, which also lists 39 linked publications.
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 18 Nov 2020.