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

NCT00250263 | Completed Phase 4

• 1 other identifier: Project 170/05
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Allergic Rhinitis; Asthma

Keywords

rhinitis; asthma; atopy; house dust mite; immunotherapy; SLIT

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (1)

• Symptom diary, medication use, visual analogue score, disease-specific rhinoconjunctivitis Quality of Life Questionnaire

  12 and 24 months

Study Arms (2)

1

PLACEBO COMPARATOR

Matching placebo- control arm (first year)

Drug: Placebo

2

ACTIVE COMPARATOR

Drug Staloral (active group)

Drug: (agent for immunotherapy) Staloral

Interventions

(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

2

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

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayside Health: lead

Study Sites (1)

The Alfred Hospital. Department of Allergy Immunology & Respiratory Medicine

Melbourne, Victoria, 3181, Australia

Location

Related Publications (4)

• 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.

  PMID: 10592467 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.

  PMID: 15298560 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.

  PMID: 11060692 BACKGROUND

• 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.

  PMID: 19696440 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic; Asthma; Rhinitis

Interventions

Pharmaceutical Preparations; Immunotherapy

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2005
• First Posted: November 8, 2005
• Study Start: November 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: February 13, 2013

Record last verified: 2005-11

Locations

AU (1)