A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy

Study Overview
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Brief Summary
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Allergic diseases represent a major health issue worldwide. Mainstay treatment is allergen avoidance and pharmacotherapy for symptom relief. Allergen immunotherapy offers the advantages of specific treatment with long lasting efficacy, and can modify the course of disease. However, use of this treatment is restricted by the high risk of adverse events especially in asthmatics. Other, better tolerated, routes of allergen administration than the current conventional subcutaneous route (SCIT) have been investigated including sublingual (SLIT). However, the immune parameters of SLIT have not been examined. We propose conducting a randomised, placebo-controlled study of a commercially-available SLIT for house dust mite (HDM) allergy to investigate induction of relevant T cell regulatory immune mechanisms. The first year will be followed by an optional open label extension period. Immunoregulatory cytokine synthesis and T cell phenotype and function (real time PCR and flow cytometry) will be examined. This project will provide important fundamental knowledge on which to base improved and greater application of this potentially curative treatment for allergy. SLIT has the potential advantage of home administration and suitability for patients with asthma who are currently unable to access many of the allergen desensitising regimens.

Official Title
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A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy

Conditions
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Allergic Rhinitis, Asthma

Intervention / Treatment
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* Drug: (agent for immunotherapy) Staloral
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: allergic rhinitis and/or mild stable asthma house dust mite allergic positive HDM-specific IgE as determined by skin prick test (wheal diameter >6 mm to D. pteronyssinus) or CAP-Pharmacia score > 2 Exclusion Criteria: Immunodeficiency diseases Severe or uncontrolled asthma Previous immunotherapy with House dust mite (HDM) extract within the last five years or ongoing immunotherapy with HDM or other allergens Continuous oral corticosteroids Subjects on treatment with beta-blockers Pregnant women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Placebo Comparator: 1<br>Matching placebo- control arm (first year) | Drug: Placebo<br>* Matching placebo for sublingual use. Same schedule used for the intervention ACTIVE group. First week (vial containing placebo) Day 1 - 1 pressure Day 2 - 2 pressures Day 3 - 4 pressures Day 4 - 6 pressures Day 5 - 8 pressures Day 6 - 10 pressures Second week (300 IR/ml) (vial containing placebo) Day 7 - 1 pressure Day 8 - 2 pressures Day 9 - 4 pressures Day 10 - 6 pressures Day 11 - 8 pressures Maintenance phase Day 12 to 364 - 8 pressures daily<br>|
| Active Comparator: 2<br>Drug Staloral (active group) | Drug: (agent for immunotherapy) Staloral<br>* Immunotherapy agent for sublingual daily use. First week (vial containing the concentration 10 IR/ml) Day 1 - 1 pressure Day 2 - 2 pressures Day 3 - 4 pressures Day 4 - 6 pressures Day 5 - 8 pressures Day 6 - 10 pressures Second week (300 IR/ml) (vial containing the concentration 300 IR/ml) Day 7 - 1 pressure Day 8 - 2 pressures Day 9 - 4 pressures Day 10 - 6 pressures Day 11 - 8 pressures Maintenance phase Day 12 to 364 - 8 pressures daily The first year will be followed by a second year open label period (optional)- 8 pressures daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological mechanisms of SLIT by phenotyping different subsets of cytokine positive T cells, regulatory T cells, and memory T cells in peripheral blood of subjects before, during and after immunotherapy. |  | 12 and 24 months | 
| -Expression of immunoregulatory cytokines by CD4+ T |  | 12 and 24 months | 
| cells |  | 12 and 24 months | 
| - Helper, regulatory and memory T cell subsets |  | 12 and 24 months | 
| (a) Helper T cells |  | 12 and 24 months | 
| (b) Regulatory T cells |  | 12 and 24 months | 
| b1- Regulatory T cell phenotype |  | 12 and 24 months | 
| b2- Regulatory T cell function |  | 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom diary, medication use, visual analogue score, disease-specific rhinoconjunctivitis Quality of Life Questionnaire |  | 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhinitis, asthma, atopy, house dust mite, immunotherapy, SLIT