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

Purpose

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.

Condition	Intervention	Phase
Allergic Rhinitis Asthma	Drug: (agent for immunotherapy) Staloral Drug: Placebo	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy

Resource links provided by NLM:

MedlinePlus related topics: Allergy Asthma

U.S. FDA Resources

Further study details as provided by Bayside Health:

Primary Outcome Measures:

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. [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
-Expression of "immunoregulatory" cytokines by CD4+ T [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
cells [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
- Helper, regulatory and memory T cell subsets [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
(a) Helper T cells [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
(b) Regulatory T cells [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
b1- Regulatory T cell phenotype [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
b2- Regulatory T cell function [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Symptom diary, medication use, visual analogue score, disease-specific rhinoconjunctivitis Quality of Life Questionnaire [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]

Enrollment:	30
Study Start Date:	November 2005
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: 1 Matching placebo- control arm (first year)	Drug: Placebo 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
Active Comparator: 2 Drug Staloral (active group)	Drug: (agent for immunotherapy) Staloral 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

Arms

Assigned Interventions

Placebo Comparator: 1

Matching placebo- control arm (first year)

Drug: Placebo

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

Active Comparator: 2

Drug Staloral (active group)

Drug: (agent for immunotherapy) Staloral

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

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00250263

Locations

Australia, Victoria
The Alfred Hospital. Department of Allergy Immunology & Respiratory Medicine
Melbourne, Victoria, Australia, 3181

Sponsors and Collaborators

Bayside Health

Investigators

Principal Investigator:	Robyn O'Hehir, MD FRACP FRCP PhD	Alfred Hospital; Monash University
Study Chair:	Jennifer Rolland, PhD	Alfred Hospital; Monash University
Study Chair:	Jo Douglass, MBBS FRACP MD	Alfred Hospital; Monash University

More Information

Publications:

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.

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.

Rolland JM, Douglass J, O'Hehir RE. Allergen immunotherapy: current and new therapeutic strategies. Expert Opin Investig Drugs. 2000 Mar;9(3):515-27. Review.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2009 Aug 20.

Responsible Party:	Bayside Health
ClinicalTrials.gov Identifier:	NCT00250263 History of Changes
Other Study ID Numbers:	Project 170/05
Study First Received:	November 6, 2005
Last Updated:	February 11, 2013
Health Authority:	Australia: National Health and Medical Research Council

Keywords provided by Bayside Health:

rhinitis
asthma
atopy

house dust mite
immunotherapy
SLIT

Additional relevant MeSH terms:

Asthma
Rhinitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity

Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on May 16, 2013