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

Study Overview
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Brief Summary
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The investigators performed open-labeled pilot study 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, causal allergen was injected into inguinal lymph node through guidance by ultrasonography three times with 4-week interval. Initial dose of allergen was 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. After the first dose, allergen concentration was escalated 3-fold at second dose, and 10-fold at third dose if there was no or mild local or systemic hypersensitivity reaction. The allergen concentration did not change at second or third dose if there was moderate local or systemic reaction. The allergen concentration was decreased by 10 or 100-fold from previous concentration if there was severe local or systemic reaction. The investigators evaluated parameters regarding allergic rhinitis within a week before the first injection and 4 months after the first injection. These parameters included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Sino-Nasal Outcome Test (SNOT-20), and 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. Skin prick test, intradermal test, blood sampling for serum allergen-specific IgE, exhaled nitric oxide, and nasal lavage for Th1, Th2, and Treg cytokines were also included. Adverse events were recorded and graded according to Muller's classification and Ring and Messmer's classification.

Official Title
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Open-labeled Pilot Study 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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* Biological: Allergen extract


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, immunosuppressant 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allergen extract<br>Causal allergen such as D. farinae (30 AU/ml), D. pteronyssinus (30 AU/ml), cat hair (10 AU/ml), dog hair/dander (1:1/10 w/v), or combination of those. Allergen extract, HollisterStier, New Orleans, USA. Intralymphatic injection in volume of 0.1 ml, three times with 4-week interval. Concentration was increased, decreased, or unchanged at 2nd or 3rd injection according to local or systemic reaction after previous injection | Biological: Allergen extract<br>* Causal allergen extract such as D. farinae, D. pteronyssinus, cat hair, dog hair/dander, or combination of those<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RQLQ | Rhinoconjunctivitis Quality of Life Questionnaire | Baseline and 4 months after the first injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNOT-20 | Sino-Nasal Outcome Test-20 | Baseline and 4 months after the first injection | 
| Skin reactivity | Allergen/histamine ratio of mean wheal diameter in skin prick test, and allergen/saline ratio of mean wheal diameter in intradermal test | Baseline and 4 months after the first injection | 
| Serum total and allergen-specific IgE and IgG4 level | Serum total and allergen-specific IgE and IgG4 level using UNICAP, Thermofisher Scientific, Sweden | Baseline and 4 months after the first injection | 
| Nasal reactivity | Symptom score and volume 2-6 cm in acoustic rhinometry during nasal provocation test with D. farinae and/or D. pteronyssinus in allergic rhinitis patients sensitized to house dust mite | Baseline and 4 months after the first injection | 
| Cytokines in nasal lavage fluid | Cytokines of Th1, Th2, and Treg in nasal lavage fluid | Baseline and 4 months after the first injection | 
| Exhaled NO | Exhaled nitric oxide measuring NIOX MINO, Thermofisher Scientific, Sweden | Baseline and 4 months after the first injection | 
| Respiratory and dermatologic symptoms provoked by allergen exposure in daily life | Visual analogue scale of respiratory and dermatologic symptoms provoked by allergen exposure in daily life (ranged from 0 to 100) | Baseline and 4 months after the first injection |