Clinical trial NCT00250263: A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy
Official title: A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Allergic Rhinitis
Asthma
Keywords: rhinitis
asthma
atopy
house dust mite
immunotherapy
SLIT
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
First posted: 2005-11-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 12 and 24 months
measure: -Expression of "immunoregulatory" cytokines by CD4+ T
timeFrame: 12 and 24 months
measure: cells
timeFrame: 12 and 24 months
measure: - Helper, regulatory and memory T cell subsets
timeFrame: 12 and 24 months
measure: (a) Helper T cells
timeFrame: 12 and 24 months
measure: (b) Regulatory T cells
timeFrame: 12 and 24 months
measure: b1- Regulatory T cell phenotype
timeFrame: 12 and 24 months
measure: b2- Regulatory T cell function
timeFrame: 12 and 24 months
Secondary outcomes:
measure: Symptom diary, medication use, visual analogue score, disease-specific rhinoconjunctivitis Quality of Life Questionnaire
timeFrame: 12 and 24 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: The Alfred Hospital. Department of Allergy Immunology & Respiratory Medicine
state: Victoria
Study officials:
affiliation: Alfred Hospital; Monash University
name: Robyn O'Hehir, MD FRACP FRCP PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alfred Hospital; Monash University
name: Jennifer Rolland, PhD
role: STUDY_CHAIR
affiliation: Alfred Hospital; Monash University
name: Jo Douglass, MBBS FRACP MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.