Promoting Tolerance to Common Allergens in High-Risk Children: Global Prevention of Asthma in Children (GPAC) Study (GPAC)

• ClinicalTrials.gov Identifier: NCT00346398
• Recruitment Status: Completed
• First Posted: June 29, 2006
• Results First Posted: December 16, 2013
• Last Update Posted: May 1, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma; Allergic Sensitization	Biological: Oral mucosal immunoprophylaxis (OMIP); Biological: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase II Multicenter, Controlled, Double-Blind Study Using Immunoprophylaxis in the Primary Prevention of Allergic Disease (ITN025AD)
• Study Start Date: May 2006
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oral mucosal immunoprophylaxis (OMIP); Participants are administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months.	Biological: Oral mucosal immunoprophylaxis (OMIP); OMIP consists of a mixture of allergen extracts including 0.2 milliliters (mL) timothy grass, 0.2 mL cat, and 0.2 mL house dust mite for a total daily dose of 0.6 mL.; Other Name: Allergen immunotherapy
Placebo Comparator: Placebo; Participants are administered, via the same route as the experimental group, an oral placebo solution daily for 12 months.	Biological: Placebo; The placebo consists of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion [ Time Frame: Three years (36 months) after Treatment Completion ]

   Allergic sensitization is defined as a positive serum allergen specific Immunoglobulin E (IgE) CAP test[1] or a positive allergy skin prick test[2]. Not experiencing allergic sensitization is the better outcome for this measure.

   1. A positive serum allergen specific IgE CAP (ImmunoCAP) test result is defined by a result >= 0.35 kU/L. Higher scores indicate greater allergic sensitization.
   2. A positive skin prick test is defined as a wheal diameter that is 3 mm larger than that produced by a negative control. Higher wheal sizes indicate greater allergic reaction or sensitization.

Secondary Outcome Measures :

1. Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion [ Time Frame: Three years (36 months) after Treatment Completion ]
   Participants who currently have asthma three years after end of treatment. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze. Current asthma is defined as a diagnosis of asthma and at least one episode of wheeze lasting 3 or more consecutive days in the past 12 months.
2. Time to First Onset of Asthma [ Time Frame: From Treatment Initiation to Month 36 Status Post Treatment Completion ]
   Time to first onset of asthma is the time from the day a participant is randomized and initiates study treatment to the diagnosis of the first of three episodes of asthma. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze.

Eligibility Criteria

• Ages Eligible for Study: 12 Months to 30 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Mount Sinai School of Medicine

New York, New York, United States, 10029

Australia, Victoria

Royal Children's Hospital

Melbourne, Victoria, Australia, 3052

Australia, Western Australia

Telethon Institute for Child Health Research

Perth, Western Australia, Australia, 6008

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

• Principal Investigator: Patrick Holt, MD; Telethon Institute for Child Health Research
• Study Chair: Peter Sly, MD; Telethon Institute for Child Health Research

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) website 

Immune Tolerance Network (ITN) website 

Study Data/Documents: Individual Participant Data Set 

Identifier: SDY545
ImmPort study identifier is SDY545.

Study summary, -design with synopsis, -adverse events, -assessment, -medications, -demographics, -lab tests, -files, et al. 

Identifier: SDY545
ImmPort study identifier is SDY545.

Individual Participant Data Set 

Identifier: ITN025AD
TrialShare is the ITN clinical trials research portal available to the public.

Study overview with synopsis, -navigator, -schedule of events, -data and reports, biospecimens and availability. 

Identifier: ITN025AD
TrialShare study identifier is ITN025AD.

Publications of Results:

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.

Other Publications:

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.

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00346398
• Other Study ID Numbers: DAIT ITN025AD
• First Posted: June 29, 2006
• Results First Posted: December 16, 2013
• Last Update Posted: May 1, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data access is provided to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

asthma; allergen; allergic disease; allergen immunotherapy; allergic sensitization; atopic dermatitis; eczema; food allergy; oral mucosal immunoprophylaxis (OMIP)

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases