Intralymphatic Immunotherapy for House Dust Mite, Dog, and Cat Allergy Using Tyrosine S® in Allergic Rhinitis (ILIT-T)
10 février 2020 mis à jour par: Sangmin Lee, MD, Gachon University Gil Medical Center
The Efficacy and Adverse Effect of Intralymphatic Immunotherapy With Tyrosine S®, Allergen Extract for Immunotherapy, in Patients With Allergic Rhinitis Induced by House Dust Mite, Dog, and Cat Allergen
The investigators will perform double-blinded placebo-controlled randomized clinical trial which evaluates the efficacy and safety of allergen-specific intralymphatic immunotherapy (ILIT) for allergens including Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), cat, and dog that are sensitized and provoke rhinitis-related symptoms in patients with allergic rhinitis (AR), using allergen extracts for allergen-specific immunotherapy (Tyrosine S, Allergy Therapeutic, West Sussex, UK).
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
After informed consent, subjects will be randomly assigned to ILIT group or placebo group in double-blind manner. In both group, causal allergen or placebo will be injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval. In ILIT group, initial dose of allergen will be 1,000-fold diluted solution from maximal concentration of allergen extract for subcutaneous immunotherapy (Tyrosine S, Allergy Therapeutic, West Sussex, UK) in volume of 0.1ml. If skin is highly reactive in skin prick test, the initial dose will be 10-fold dilution from maximal concentration where diameter of wheal is less than that of histamine. After the first dose, allergen concentration will be escalated 3-fold at second dose, and 10-fold at third dose if there are no (or mild) local or systemic hypersensitivity reaction. The allergen concentration will not change at second or third dose if there is moderate local or systemic reaction. The allergen concentration will decrease by 10 or 100-fold from previous concentration or further injection will be held if there is severe local or systemic reaction after sufficient explanation and discussion with subjects.
The investigators will evaluate allergic rhinitis symptom score before and 4, 12 months after the initial treatment. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Sino-Nasal Outcome Test (SNOT-20) will be used. Visual analogue scale (VAS) of symptoms including rhinorrhea, sneezing, nasal obstruction, postnasal drip, eye/nose/ear/palate itching, dyspnea, wheezing, chest discomfort as well as urticaria, angioedema, and itching on exposed skin during exposure to causal allergen in daily life will be also evaluated. Skin prick test (SPT), intradermal test (IDT), blood sampling for serum total immunoglobulin E (IgE), allergen-specific IgE, and allergen-specific immunoglobulin G4 (IgG4), nasal lavage for Th1, Th2, and Treg cytokines, and nasal provocation test (NPT) with Df and/or Dp allergen (in subjects whose AR symptoms are provoked by Df and/or Dp) will be also performed before and 4, 12 months after the initial treatment. In addition, the investigators evaluated the change of subjects' recognition of causal allergens, their avoidance, and AIT during this study. Using VAS, subjects were requested to score the rate of agreement with "Allergen provokes allergic symptoms in daily life", "Allergen avoidance can reduce allergic symptoms", "Allergen-specific Immunotherapy (AIT) can reduce allergic symptoms", "I can pay 50,000 Korean Won (KRW)/month for allergen avoidance", "I can pay 100,000 KRW/month for allergen avoidance", "I can pay 200,000 KRW/month for allergen avoidance", "I can pay 150,000 KRW for each injection of ILIT", "I can pay 300,000 KRW for each injection of ILIT", "I can pay 600,000 KRW for each injection of ILIT" before and after SPT/IDT, after NPT, 4 months and 1 year after ILIT.
Adverse events will be recorded and graded according to Muller classification and Ring and Meissner classification.
Type d'étude
Interventionnel
Inscription (Réel)
32
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Incheon, Corée, République de, 405-760
- Gachon University Gil Medical Center
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
19 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
We enrolled subjects who suffered from AR, symptoms of which were provoked by Dp, Df, dog, and/or cat allergen. Concretely, two inclusion criteria should be met.
- Sensitization should be verified by skin prick test and the level of serum specific IgE measured by ImmunoCAP® (Thermo Fisher Scientific, Uppsala, Sweden).
- Subjects should complain of AR symptoms during exposure of house dust, dog and/or cat in daily life.
Exclusion Criteria:
- Uncontrolled or severe asthma according to Global Initiative of Asthma (GINA) guideline including a case in which forced expiratory volume in 1 s (FEV1) was less than 50% of predicted value
- Significant cardiovascular, hepatic, renal, hematologic, oncologic, or infectious diseases
- Administration of beta blocker, angiotensin converting enzyme inhibitor, tricyclic antidepressant, immunosuppressant including systemic glucocorticosteroid within last 2 weeks
- AR caused by other perennial or seasonal allergen
- Prior history of allergen-specific immunotherapy
- Rejection or low compliance,
- Pregnancy or lactation
- Vulnerable volunteer
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Active group
In active group, extract of causal allergen will be injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval.
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0.5 ml of allergen extract from D. farinae, D. pteronyssinus, cat, and/or dog for allergen specific immunotherapy (Tyrosine S, Allergy Therapeutic, UK) will be injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval.
Autres noms:
Subjects are requested to administer oral antihistamine (cetirizine) or nasal glucocorticosteroid (ciclesonide) as rescue medication for allergic rhinitis in accordance with severity and frequency of allergic rhinitis symptoms according to Allergic Rhinitis and its Impact on Asthma (ARIA) guideline.
Autres noms:
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Comparateur placebo: Placebo group
In placebo group, normal saline will be injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval.
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Subjects are requested to administer oral antihistamine (cetirizine) or nasal glucocorticosteroid (ciclesonide) as rescue medication for allergic rhinitis in accordance with severity and frequency of allergic rhinitis symptoms according to Allergic Rhinitis and its Impact on Asthma (ARIA) guideline.
Autres noms:
0.5 ml of normal saline will be injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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RQLQ
Délai: 4 months after the day of first injection of ILIT
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Rhinoconjunctivitis Quality of Life Questionnaires
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4 months after the day of first injection of ILIT
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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SNOT-20
Délai: before and 4, 12 months after the day of first injection of ILIT
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Sinonasal Outcome Test-20
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before and 4, 12 months after the day of first injection of ILIT
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Allergic symptoms provoked by causal allergen in daily life
Délai: before and 4, 12 months after the day of first injection of ILIT
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Rates scored by subjects using visual analogue scale regarding allergic symptoms provoked by causal allergen in daily life
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before and 4, 12 months after the day of first injection of ILIT
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Rhinitis symptom in nasal provocation test
Délai: before and 4, 12 months after the day of first injection of ILIT
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Rhinitis symptom (visual analogue scale: 0~100) during nasal provocation test with allergen of D. farinae and/or D. pteronyssinus in subjects in whom D. farinae and/or D. pteronyssinus is causal allergen.
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before and 4, 12 months after the day of first injection of ILIT
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Skin reactivity in skin prick test
Délai: before and 4, 12 months after the day of first injection of ILIT
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Mean diameters of wheal caused by 1- to 10^7- fold dilution of causal allergen in skin prick test and their allergen histamine ratio
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before and 4, 12 months after the day of first injection of ILIT
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Skin reactivity in intradermal test
Délai: before and 4, 12 months after the day of first injection of ILIT
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Mean diameters of wheal caused by 10^2- to 10^7- fold dilution of causal allergen in intradermal test and their allergen saline ratio
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before and 4, 12 months after the day of first injection of ILIT
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Serum total IgE level
Délai: before and 4, 12 months after the day of first injection of ILIT
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Serum total IgE level using ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden)
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before and 4, 12 months after the day of first injection of ILIT
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Allergen-specific IgE for causal allergen
Délai: before and 4, 12 months after the day of first injection of ILIT
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Allergen-specific IgE for causal allergen of D. farinae, D. pteronyssinus, cat, and/dog using ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden)
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before and 4, 12 months after the day of first injection of ILIT
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Cytokines in nasal lavage fluid before and after nasal provocation test
Délai: before and 4, 12 months after the day of first injection of ILIT
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Cytokines of Th1, Th2, and Treg immunity including interleukin-4 (IL-4), IL-5, IL-10, IL-12, IL-13, interferon-gamma (IFN-g), and tumor growth factor-beta (TGF-b) in nasal lavage fluid
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before and 4, 12 months after the day of first injection of ILIT
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Subjects' score (0~100) regarding agreement to "Allergen provokes allergic symptoms in daily life"
Délai: before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Subjects' score regarding agreement to "Allergen provokes allergic symptoms in daily life" using visual analogue scale (0~100).
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before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Subjects' score (0~100) regarding agreement to "Allergen avoidance can reduce allergic symptoms"
Délai: before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Subjects' score regarding agreement to "Allergen avoidance can reduce allergic symptoms" using visual analogue scale (0~100).
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before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Subjects' score (0~100) regarding agreement to "Allergen-specific immunotherapy can reduce allergic symptoms"
Délai: before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Subjects' score regarding agreement to "Allergen-specific immunotherapy can reduce allergic symptoms" using visual analogue scale (0~100).
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before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Willingness to pay for allergen avoidance
Délai: before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Agreement% scored by subjects using visual analogue scale to "I am willing to pay 50,000, 100,000 or 200,000 Korean Won per month for allergen avoidance"
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before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Willingness to pay for intralymphatic immunotherapy
Délai: before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Agreement% scored by subjects using visual analogue scale to "I am willing to pay 150,000, 300,000 or 600,000 Korean Won for each injection of intralymphatic immunotherapy"
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before skin prick test / intradermal test, nasal provocation test, and 4, 12 months after the day of first injection of ILIT
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Nasal mucosal inflammation
Délai: before and 4, 12 months after the day of first injection of ILIT
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Inflammatory cell count in nasal mucosal biopsy (/high power field, x400)
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before and 4, 12 months after the day of first injection of ILIT
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RQLQ
Délai: 12 months after the day of first injection of ILIT
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Rhinoconjunctivitis Quality of Life Questionnaires
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12 months after the day of first injection of ILIT
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Nasal cavitary volume decrease in nasal provocation test
Délai: before and 4, 12 months after the day of first injection of ILIT
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Nasal cavitary volume decrease (basal%) measured by acoustic rhinometry during nasal provocation test with allergen of D. farinae and/or D. pteronyssinus in subjects in whom D. farinae and/or D. pteronyssinus is causal allergen.
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before and 4, 12 months after the day of first injection of ILIT
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Allergen-specific IgG4 for causal allergen
Délai: before and 4, 12 months after the day of first injection of ILIT
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Allergen-specific IgG4 for causal allergen of D. farinae, D. pteronyssinus, cat, and/dog using ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden)
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before and 4, 12 months after the day of first injection of ILIT
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Sang Min Lee, MD, PhD, Gachon University Gil Medical Center
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wuthrich B, Crameri R, Graf N, Johansen P, Kundig TM. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17908-12. doi: 10.1073/pnas.0803725105. Epub 2008 Nov 10.
- Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013 Feb;131(2):412-20. doi: 10.1016/j.jaci.2012.10.056.
- Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013 Nov;132(5):1248-1252.e5. doi: 10.1016/j.jaci.2013.07.033. Epub 2013 Sep 13. No abstract available.
- Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009 Dec;9(6):537-43. doi: 10.1097/ACI.0b013e3283310ff7.
- Kundig TM, Johansen P, Bachmann MF, Cardell LO, Senti G. Intralymphatic immunotherapy: time interval between injections is essential. J Allergy Clin Immunol. 2014 Mar;133(3):930-1. doi: 10.1016/j.jaci.2013.11.036. Epub 2014 Jan 15. No abstract available.
- Zaleska A, Eiwegger T, Soyer O, van de Veen W, Rhyner C, Soyka MB, Bekpen C, Demiroz D, Treis A, Sollner S, Palomares O, Kwok WW, Rose H, Senti G, Kundig TM, Ozoren N, Jutel M, Akdis CA, Crameri R, Akdis M. Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine. Allergy. 2014 Sep;69(9):1162-70. doi: 10.1111/all.12461. Epub 2014 Jul 12. Erratum In: Allergy. 2016 Jan;71(1):129.
- Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM, Graf N, Steiner M, Hothorn LA, Gronlund H, Tivig C, Zaleska A, Soyer O, van Hage M, Akdis CA, Akdis M, Rose H, Kundig TM. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012 May;129(5):1290-6. doi: 10.1016/j.jaci.2012.02.026. Epub 2012 Mar 30.
- Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy: from the rationale to human applications. Curr Top Microbiol Immunol. 2011;352:71-84. doi: 10.1007/82_2011_133.
- Johansen P, Kundig TM. Intralymphatic immunotherapy and vaccination in mice. J Vis Exp. 2014 Feb 2;(84):e51031. doi: 10.3791/51031.
- Graf N, Dinkel B, Rose H, Hothorn LA, Gerhard D, Johansen P, Kundig TM, Klimek L, Senti G. A critical appraisal of analyzing nasal provocation test results in allergen immunotherapy trials. Rhinology. 2014 Jun;52(2):137-41. doi: 10.4193/Rhino13.145.
- Senti G, Kundig TM. Intralymphatic immunotherapy. World Allergy Organ J. 2015 Mar 7;8(1):9. doi: 10.1186/s40413-014-0047-7. eCollection 2015.
- Hjalmsdottir A, Wackerle-Men Y, Duda A, Kundig TM, Johansen P. Dosing intervals in intralymphatic immunotherapy. Clin Exp Allergy. 2016 Mar;46(3):504-7. doi: 10.1111/cea.12657. No abstract available.
- Patterson AM, Bonny AE, Shiels WE 2nd, Erwin EA. Three-injection intralymphatic immunotherapy in adolescents and young adults with grass pollen rhinoconjunctivitis. Ann Allergy Asthma Immunol. 2016 Feb;116(2):168-70. doi: 10.1016/j.anai.2015.11.010. Epub 2015 Dec 17. No abstract available.
- Park HJ, Kim SH, Shin YS, Park CH, Cho ES, Choi SJ, Park SH, Jung JH, Kang IG, Lee MS, Kim DW, Lee SM, Yang MS, Lee SP. Intralymphatic immunotherapy with tyrosine-adsorbed allergens: a double-blind, placebo-controlled trial. Respir Res. 2021 Jun 4;22(1):170. doi: 10.1186/s12931-021-01766-0.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
1 juillet 2016
Achèvement primaire (Réel)
1 décembre 2019
Achèvement de l'étude (Réel)
1 janvier 2020
Dates d'inscription aux études
Première soumission
10 janvier 2016
Première soumission répondant aux critères de contrôle qualité
24 janvier 2016
Première publication (Estimation)
28 janvier 2016
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
11 février 2020
Dernière mise à jour soumise répondant aux critères de contrôle qualité
10 février 2020
Dernière vérification
1 février 2020
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- GBIRB2016-002
Plan pour les données individuelles des participants (IPD)
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