Clinical trial NCT00346398: Promoting Tolerance to Common Allergens in High-Risk Children: Global Prevention of Asthma in Children (GPAC) Study
Official title: A Phase II Multicenter, Controlled, Double-Blind Study Using Immunoprophylaxis in the Primary Prevention of Allergic Disease (ITN025AD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Allergic Sensitization
Keywords: asthma
allergen
allergic disease
allergen immunotherapy
allergic sensitization
atopic dermatitis
eczema
food allergy
oral mucosal immunoprophylaxis (OMIP)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2006-06-29
Enrollment: 51
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether early childhood exposure to common allergens (substances that can trigger allergies and asthma) can prevent the development of asthma in children at high risk for developing the disease.

Detailed description: Researchers suspect that allergies to common inhaled allergens (such as house dust mite, cat dander, and grass pollens) are a major cause of childhood asthma. Recent evidence suggests that if allergies to inhaled allergens are prevented, this can cause changes in the immune system that may inhibit the development of asthma. Although strategies to prevent allergies generally focus on avoiding the allergen, complete avoidance of the common allergens linked to asthma would require extreme measures and is impractical.

Oral mucosal immunoprophylaxis (OMIP) therapy is an allergy treatment that can induce long-lasting immune tolerance in people already suffering from allergies. By exposing the patient to small, repeated, but increasing doses of the problem allergen over a long period of time, the patient's immune system is eventually desensitized to that particular allergen. OMIP therapy has been shown to be safe in children as young as 2 years old. This study will evaluate if OMIP therapy against common inhaled allergens is safe and effective in preventing the development of asthma in children at high risk for developing the disease. Children enrolled in this study have been diagnosed with eczema or food allergies and have a family history of eczema, allergic rhinitis, or asthma.

There are two groups in this study. The experimental arm participants will receive OMIP therapy (a mixture of house dust mite, cat, and timothy grass allergens) as daily oral drops under the tongue for 1 year; Placebo arm participants will receive an allergen free placebo solution. Participants will be followed for an additional 3 years to see whether they develop allergies or asthma and to determine how OMIP affects their immune system's response to allergens. There will be 5 study visits in the first year and 6 visits over the next 3 years. At all visits, participants will be assessed for allergy/asthma symptoms, will be asked to complete questionnaires, and may be asked to provide blood or saliva samples.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with eczema (atopic dermatitis)
* Family history of eczema, allergic rhinitis, or asthma
* Allergy to one or more of the following: egg white, cow's milk, peanut, or soybean
* Weigh at least 9.5 kg (20.9 lbs)
* Parent or guardian willing to provide informed consent

Exclusion Criteria:

* Allergy to house dust mite, cat, or timothy grass
* Born prematurely (before 36th week's gestation)
* Previous diagnosis of asthma OR have had 3 or more distinct episodes of wheeze during the first year of life
* Chronic pulmonary disease
* Chronic disease requiring therapy
* Past or current treatment with systemic immunomodulator medication
* Past or current treatment with allergen-specific immunotherapy
* Received 10 or more days of systemic steroids in the 3 months prior to study entry
* Orofacial abnormalities that are likely to interfere with the subject's ability to take study treatment
* Participated in another clinical study within the 3 months prior to study entry

Primary outcomes:
measure: Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion
timeFrame: Three years (36 months) after Treatment Completion
Secondary outcomes:
measure: Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion
timeFrame: Three years (36 months) after Treatment Completion
measure: Time to First Onset of Asthma
timeFrame: From Treatment Initiation to Month 36 Status Post Treatment Completion
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Telethon Institute for Child Health Research
state: Western Australia
Study officials:
affiliation: Telethon Institute for Child Health Research
name: Patrick Holt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Telethon Institute for Child Health Research
name: Peter Sly, MD
role: STUDY_CHAIR
References:
citation: Mascarell L, Van Overtvelt L, Moingeon P. Novel ways for immune intervention in immunotherapy: mucosal allergy vaccines. Immunol Allergy Clin North Am. 2006 May;26(2):283-306, vii-viii. doi: 10.1016/j.iac.2006.02.009.
citation: Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol. 2006 May;117(5):1047-53. doi: 10.1016/j.jaci.2005.12.1306. Epub 2006 Mar 6.
citation: Holt PG, Sly PD, Sampson HA, Robinson P, Loh R, Lowenstein H, Calatroni A, Sayre P. Prophylactic use of sublingual allergen immunotherapy in high-risk children: a pilot study. J Allergy Clin Immunol. 2013 Oct;132(4):991-3.e1. doi: 10.1016/j.jaci.2013.04.049. Epub 2013 Jun 12. No abstract available.