Intralymphatic Immunotherapy (ILIT) for House Dust Mite, Cat, and Dog Allergen in Allergic Rhinitis Patients

Study Overview
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Brief Summary
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We 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.

Detailed Description
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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 (30 AU/ml for Df or Dp, 10 AU/ml for Cat hair, and 1:1/10 weight/volume for dog hair/dander, HollisterStier, New Orleans, USA) 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 local or systemic hypersensitivity reaction. The allergen concentration will not change at second or third dose if there is mild local or systemic reaction. The allergen concentration will decrease by 10 or 100-fold from previous concentration or further injection will be holded 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, intradermal test, blood sampling for serum allergen-specific IgE, exhaled nitric oxide, and nasal lavage for Th1, Th2, and Treg cytokines will be also performed before and 4, 12 months after the initial treatment. Adverse events will be recorded and graded according to Muller classification and Ring and Messner classification.

Official Title
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A Double-blinded Placebo-controlled Randomized Clinical Trial Evaluating the Efficacy and Adverse Effect of Intralymphatic Immunotherapy (ILIT) for House Dust Mite, Cat, and Dog Allergen in Allergic Rhinitis Patients

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Drug: HollisterStier
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Allergic rhinitis to house dust mite (Df, Dp), cat or dog More than 3mm reaction at skin prick test for Df, Dp, cat or dog or more than class 3 at serum specific IgE level (UNICAP or MAST) Exclusion Criteria: Uncontrolled or severe asthma according to Global Initiative of Asthma (GINA) guideline FEV1 less than 50% of predicted value if there is comorbid asthma. Subject rejects the enrollment into study Low compliance Pregnancy or lactation Significant cardiovascular, hepatic, renal, hematologic, oncologic, or infectious diseases Administration of beta blocker, angiotensin converting enzyme inhibitor, tricyclic antidepressant, immnosuppressant including systemic glucocorticosteroid (20mg or more dose of prednisolone or equivalent dose of other steroid) within last 2 weeks Prior history of allergen-specific immunotherapy Allergic rhinitis caused by other perennial or seasonal allergen Vulnerable volunteer

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Allergen extract<br>0.1 ml of allergen extracts | Drug: HollisterStier<br>* 0.1 ml of 30 AU/ml for Df or Dp, 10 AU/ml for Cat hair, and/or 1:1/10 weight/volume for dog hair/dander 3 injections into an inguinal lymph node<br>* Other names: Allergen extracts, New Orleans, USA;|
| Placebo Comparator: Placebo<br>Normal saline, 0.1 ml | Drug: Normal saline<br>* 0.1 ml of normal saline 3 injections into an inguinal lymph node<br>* Other names: JW-pharma, Seoul, Republic of Korea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rhinoconjunctivitis Quality of Life Questionnaire |  | up to 12 months after the initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNOT-20 | Sino-Nasal Outcome Test | before and 4, 12 months after the initial treatment | 
| Skin reactivity | Diameters of wheal provoked by causal allergens in skin prick test and intradermal test | before and 4, 12 months after the initial treatment | 
| Serum alllergen-specific IgE level | Serum alllergen-specific IgE level using UNICAP, Thermofisher Scientific, Sweden | before and 4, 12 months after the initial treatment | 
| Nasal reactivity | Threshold concentration in nasal provocation test for allergens of Df and Dp | before and 4, 12 months after the initial treatment | 
| Cytokines in nasal lavage fluid | Cytokines of Th1, Th2, and Treg in nasal lavage fluid | before and 4, 12 months after the initial treatment | 
| Exhaled NO | Exhaled nitric oxide measuring NIOX MINO, Thermofisher Scientific, Sweden | before and 4, 12 months after the initial treatment | 
| Allergic rhinitis symptoms during allergen exposure in daily life | Visual analog scare of allergic rhinitis symptoms during allergen exposure in daily life | before and 4, 12 months after the initial treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergic rhinitis, immunotherapy