Determination of Specific Biomarkers of Acute Attack of Angioedema Within Pediatric Population
NCT ID: NCT02854397
Last Updated: 2020-11-18
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
TERMINATED
Total Enrollment
31 participants
Study Classification
OBSERVATIONAL
Study Start Date
2016-02-15
Study Completion Date
2020-06-30
Brief Summary
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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).
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).
Detailed Description
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Conditions
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Hereditary Angioedema
Healthy Volunteers
Study Design
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Observational Model Type
OTHER
Study Time Perspective
PROSPECTIVE
Study Groups
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patients with hereditary angioedema
A blood sample will be performed in crisis and 7 days after the crisis.
blood sample
Intervention Type
OTHER
patients with angioedema resulting of mast cell activation
A blood sample will be performed in crisis and 7 days after the crisis.
blood sample
Intervention Type
OTHER
healthy patients, without angioedema
A quantity of additional blood was taken from eligible patients who had a scheduled blood sample.
blood sample
Intervention Type
OTHER
Interventions
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blood sample
Intervention Type
OTHER
Eligibility Criteria
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Inclusion Criteria
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,
* 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).
* 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,
* 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).
Exclusion Criteria
* 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.
* 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.
Minimum Eligible Age
1 Year
Maximum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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University Hospital, Grenoble
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Anne Pagnier
Role: PRINCIPAL_INVESTIGATOR
University Hospital, Grenoble
Locations
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University hospital angers
Angers, , France
Site Status
University Hospital Besançon
Besançon, , France
Site Status
University hospital Bordeaux
Bordeaux, , France
Site Status
University hopital Clermont-Ferrand
Clermont-Ferrand, , France
Site Status
University Hospital Grenoble
Grenoble, , France
Site Status
University Hospital Lille
Lille, , France
Site Status
University Hospital Lyon
Lyon, , France
Site Status
University hospital Marseille
Marseille, , France
Site Status
University hospital Montpellier
Montpellier, , France
Site Status
University hospital Nancy
Nancy, , France
Site Status
General Hospital
Niort, , France
Site Status
university hospital Saint-Antoine (AP-HP)
Paris, , France
Site Status
University hospital Rouen
Rouen, , France
Site Status
University hospital Toulouse
Toulouse, , France
Site Status
Countries
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France
References
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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.
Reference Type
BACKGROUND
Pagnier 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.
Reference Type
BACKGROUND
Dinkel 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.
Reference Type
BACKGROUND
Bygum 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.
Reference Type
BACKGROUND
Farkas 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.
Reference Type
BACKGROUND
El-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.
Reference Type
BACKGROUND
Farkas 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.
Reference Type
BACKGROUND
Sanchez 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.
Reference Type
BACKGROUND
Pritzker 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.
Reference Type
BACKGROUND
Parisi 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
Reference Type
BACKGROUND
MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol. 2014 Aug;25(5):420-7. doi: 10.1111/pai.12168. Epub 2013 Dec 9.
Reference Type
BACKGROUND
Deroux 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.
Reference Type
BACKGROUND
Cugno 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.
Reference Type
BACKGROUND
Hogan AD, Schwartz LB. Markers of mast cell degranulation. Methods. 1997 Sep;13(1):43-52. doi: 10.1006/meth.1997.0494.
Reference Type
BACKGROUND
Brickman 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.
Reference Type
BACKGROUND
Payne V, Kam PC. Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia. 2004 Jul;59(7):695-703. doi: 10.1111/j.1365-2044.2004.03757.x.
Reference Type
BACKGROUND
Kasperska-Zajac A, Grzanka A, Czecior E, Misiolek M, Rogala B, Machura E. Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria/angioedema and after aspirin challenge. J Eur Acad Dermatol Venereol. 2013 Aug;27(8):1048-52. doi: 10.1111/j.1468-3083.2012.04486.x. Epub 2012 Feb 21.
Reference Type
BACKGROUND
Fujii K, Konishi K, Kanno Y, Ohgou N. Acute urticaria with elevated circulating interleukin-6 is resistant to anti-histamine treatment. J Dermatol. 2001 May;28(5):248-50. doi: 10.1111/j.1346-8138.2001.tb00126.x.
Reference Type
BACKGROUND
Kasperska-Zajac A, Brzoza Z. Increased D-dimer concentration in plasma of patients with severe acute urticaria. Br J Dermatol. 2009 Dec;161(6):1409-10. doi: 10.1111/j.1365-2133.2009.09466.x. Epub 2009 Sep 15. No abstract available.
Reference Type
BACKGROUND
Brevet: w/o 2008 062314 circulating ve-cadherin as a predictive marker of sensitivity or resistance to anti-tumoral treatment, and improved method for the detection of soluble proteins.
Reference Type
BACKGROUND
Bouillet L, Sidibe A, Polena H, Mannic T, Deroux A, Stidder B, Vittecoq O, Vilgrain I. [Endothelial junctions: exploiting their instability in the development of biomarkers for vascular remodelling]. Med Sci (Paris). 2014 Jun-Jul;30(6-7):633-5. doi: 10.1051/medsci/20143006012. Epub 2014 Jul 11. No abstract available. French.
Reference Type
BACKGROUND
Bouillet L, Vilgrain I. VE-cadherin, a potential marker for endothelial cell activation during hereditary angioedema attacks. J Allergy Clin Immunol. 2014 Jul;134(1):241. doi: 10.1016/j.jaci.2014.04.016. Epub 2014 May 27. No abstract available.
Reference Type
BACKGROUND
Sidibe A, Polena H, Pernet-Gallay K, Razanajatovo J, Mannic T, Chaumontel N, Bama S, Marechal I, Huber P, Gulino-Debrac D, Bouillet L, Vilgrain I. VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs. Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H455-63. doi: 10.1152/ajpheart.00774.2013. Epub 2014 May 23.
Reference Type
BACKGROUND
Sidibe A, Polena H, Razanajatovo J, Mannic T, Chaumontel N, Bama S, Marechal I, Huber P, Gulino-Debrac D, Bouillet L, Vilgrain I. Dynamic phosphorylation of VE-cadherin Y685 throughout mouse estrous cycle in ovary and uterus. Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H448-54. doi: 10.1152/ajpheart.00773.2013. Epub 2014 May 23.
Reference Type
BACKGROUND
Bouillet L, Mannic T, Arboleas M, Subileau M, Massot C, Drouet C, Huber P, Vilgrain I. Hereditary angioedema: key role for kallikrein and bradykinin in vascular endothelial-cadherin cleavage and edema formation. J Allergy Clin Immunol. 2011 Jul;128(1):232-4. doi: 10.1016/j.jaci.2011.02.017. Epub 2011 Mar 24. No abstract available.
Reference Type
BACKGROUND
Suffritti C, Zanichelli A, Maggioni L, Bonanni E, Cugno M, Cicardi M. High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency. Clin Exp Allergy. 2014 Dec;44(12):1503-14. doi: 10.1111/cea.12293.
Reference Type
BACKGROUND
Kahn R, Herwald H, Muller-Esterl W, Schmitt R, Sjogren AC, Truedsson L, Karpman D. Contact-system activation in children with vasculitis. Lancet. 2002 Aug 17;360(9332):535-41. doi: 10.1016/S0140-6736(02)09743-X.
Reference Type
BACKGROUND
Ghannam A, Sellier P, Defendi F, Favier B, Charignon D, Lopez-Lera A, Lopez-Trascasa M, Ponard D, Drouet C. C1 inhibitor function using contact-phase proteases as target: evaluation of an innovative assay. Allergy. 2015 Sep;70(9):1103-11. doi: 10.1111/all.12657. Epub 2015 Jun 9.
Reference Type
BACKGROUND
Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future prospects. Blood. 2009 Mar 26;113(13):2878-87. doi: 10.1182/blood-2008-06-165845. Epub 2008 Nov 13.
Reference Type
BACKGROUND
Blohme G. Treatment of hereditary angioneurotic oedema with tranexamic acid. A random double-blind cross-over study. Acta Med Scand. 1972 Oct;192(4):293-8. doi: 10.1111/j.0954-6820.1972.tb04818.x. No abstract available.
Reference Type
BACKGROUND
Brown NJ, Gainer JV, Stein CM, Vaughan DE. Bradykinin stimulates tissue plasminogen activator release in human vasculature. Hypertension. 1999 Jun;33(6):1431-5. doi: 10.1161/01.hyp.33.6.1431.
Reference Type
BACKGROUND
Cugno M, Hack CE, de Boer JP, Eerenberg AJ, Agostoni A, Cicardi M. Generation of plasmin during acute attacks of hereditary angioedema. J Lab Clin Med. 1993 Jan;121(1):38-43.
Reference Type
BACKGROUND
Frank MM, Sergent JS, Kane MA, Alling DW. Epsilon aminocaproic acid therapy of hereditary angioneurotic edema. A double-blind study. N Engl J Med. 1972 Apr 13;286(15):808-12. doi: 10.1056/NEJM197204132861503. No abstract available.
Reference Type
BACKGROUND
Joseph K, Tholanikunnel BG, Wolf B, Bork K, Kaplan AP. Deficiency of plasminogen activator inhibitor 2 in plasma of patients with hereditary angioedema with normal C1 inhibitor levels. J Allergy Clin Immunol. 2016 Jun;137(6):1822-1829.e1. doi: 10.1016/j.jaci.2015.07.041. Epub 2015 Sep 26.
Reference Type
BACKGROUND
Kaplan AP, Austen KF. A prealbumin activator of prekallikrein. II. Derivation of activators of prekallikrein from active Hageman factor by digestion with plasmin. J Exp Med. 1971 Apr 1;133(4):696-712. doi: 10.1084/jem.133.4.696.
Reference Type
BACKGROUND
Kleniewski J, Blankenship DT, Cardin AD, Donaldson V. Mechanism of enhanced kinin release from high molecular weight kininogen by plasma kallikrein after its exposure to plasmin. J Lab Clin Med. 1992 Jul;120(1):129-39.
Reference Type
BACKGROUND
Kluft C, Trumpi-Kalshoven MM, Jie AF, Veldhuyzen-Stolk EC. Factor XII-dependent fibrinolysis: a double function of plasma kallikrein and the occurrence of a previously undescribed factor XII- and kallikrein-dependent plasminogen proactivator. Thromb Haemost. 1979 Jun 30;41(4):756-73.
Reference Type
BACKGROUND
Nielsen EW, Johansen HT, Hogasen K, Wuillemin W, Hack CE, Mollnes TE. Activation of the complement, coagulation, fibrinolytic and kallikrein-kinin systems during attacks of hereditary angioedema. Scand J Immunol. 1996 Aug;44(2):185-92. doi: 10.1046/j.1365-3083.1996.d01-298.x.
Reference Type
BACKGROUND
Reshef A, Zanichelli A, Longhurst H, Relan A, Hack CE. Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk. Allergy. 2015 May;70(5):506-13. doi: 10.1111/all.12587. Epub 2015 Feb 23.
Reference Type
BACKGROUND
Other Identifiers
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38RC15.180
Identifier Type: -
Identifier Source: org_study_id