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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Placebo Comparator | Matching placebo- control arm (first year) |
|
| 2 | Active Comparator | Drug Staloral (active group) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| (agent for immunotherapy) Staloral | Drug | 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Symptom diary, medication use, visual analogue score, disease-specific rhinoconjunctivitis Quality of Life Questionnaire | 12 and 24 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robyn O'Hehir, MD FRACP FRCP PhD | Alfred Hospital; Monash University | Principal Investigator |
| Jennifer Rolland, PhD | Alfred Hospital; Monash University | Study Chair |
| Jo Douglass, MBBS FRACP MD | Alfred Hospital; Monash University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Alfred Hospital. Department of Allergy Immunology & Respiratory Medicine | Melbourne | Victoria | 3181 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10592467 | Background | Fanta C, Bohle B, Hirt W, Siemann U, Horak F, Kraft D, Ebner H, Ebner C. Systemic immunological changes induced by administration of grass pollen allergens via the oral mucosa during sublingual immunotherapy. Int Arch Allergy Immunol. 1999 Nov;120(3):218-24. doi: 10.1159/000024270. | |
| 15298560 | Background | Gardner LM, Thien FC, Douglass JA, Rolland JM, O'Hehir RE. Induction of T 'regulatory' cells by standardized house dust mite immunotherapy: an increase in CD4+ CD25+ interleukin-10+ T cells expressing peripheral tissue trafficking markers. Clin Exp Allergy. 2004 Aug;34(8):1209-19. doi: 10.1111/j.1365-2222.2004.02009.x. |
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| ID | Term |
|---|---|
| D065631 | Rhinitis, Allergic |
| D001249 | Asthma |
| D012220 | Rhinitis |
| ID | Term |
|---|---|
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
| D010038 | Otorhinolaryngologic Diseases |
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| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
| D007167 | Immunotherapy |
| ID | Term |
|---|---|
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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|
| Placebo | Drug | 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 |
|
| 11060692 | Background | Rolland JM, Douglass J, O'Hehir RE. Allergen immunotherapy: current and new therapeutic strategies. Expert Opin Investig Drugs. 2000 Mar;9(3):515-27. doi: 10.1517/13543784.9.3.515. |
| 19696440 | Derived | O'Hehir RE, Gardner LM, de Leon MP, Hales BJ, Biondo M, Douglass JA, Rolland JM, Sandrini A. House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells. Am J Respir Crit Care Med. 2009 Nov 15;180(10):936-47. doi: 10.1164/rccm.200905-0686OC. Epub 2009 Aug 20. |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D001982 | Bronchial Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |