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

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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:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Asthma
Allergic Sensitization
Interventions Biological: Oral mucosal immunoprophylaxis (OMIP)
Biological: Placebo
Enrollment 51
Recruitment Details Subject recruitment occurred between June 2006 and July 2007 at 2 sites in Australia and 1 site in the United States
Pre-assignment Details At a screening visit, subjects underwent procedures to establish that all inclusion criteria were met and none of the exclusion criteria were met. All guardians provided written informed consent
Arm/Group Title OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Hide Arm/Group Description Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted 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. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma. Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Period Title: Overall Study
Started 25 26
Completed 22 24
Not Completed 3 2
Reason Not Completed
Lost to Follow-up             3             0
Withdrawal by Subject             0             2
Arm/Group Title OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo Total
Hide Arm/Group Description Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted 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. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma. Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma. Total of all reporting groups
Overall Number of Baseline Participants 25 26 51
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 51 participants
Aged 12-17 Months 6 6 12
Aged 18-23 Months 16 12 28
Aged 24-30 Months 3 8 11
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 51 participants
Female
13
  52.0%
12
  46.2%
25
  49.0%
Male
12
  48.0%
14
  53.8%
26
  51.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 51 participants
United States 4 4 8
Australia 21 22 43
Severity of Atopic Dermatitis (AD) Using SCORAD Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a Scale
Number Analyzed 25 participants 26 participants 51 participants
13.3  (8.5) 11.4  (9.1) 12.3  (8.8)
[1]
Measure Description: Scoring of Atopic Dermatitis (SCORAD) disease-severity scale measures intensity of erythema, edema/papulation, oozing/crusts, excoriations, lichenification and dryness, each on a scale from 0-3 for a maximum total of 18 points. This score is multiplied by 3.5 and added to 1/5 of the affected percent body surface area. The final score is added to the score from a 0-10 point pruritus visual analog scale (VAS) and a 0-10 point loss of sleep VAS. Summary: SCORAD (0-103)=extent (0-100)/5+intensity (0-18)x3.5 + pruritus and sleep (0-20).Interpretation: SCORAD (0 (no disease) to 103 (most severe)).
1.Primary Outcome
Title Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion
Hide Description

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.
Time Frame Three years (36 months) after Treatment Completion
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat minus one participant in placebo group who had a sibling in trial
Arm/Group Title OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Hide Arm/Group Description:
Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted 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. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Unit of Measure: participants
22 19
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMIP With Timothy Grass, Cat and House Dust Mite Allergens, Placebo
Comments Participants who drop out (have missing efficacy endpoints) are considered treatment failures.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments Odds Ratios are calculated using a logistic regression with a Wald chi square test. Experimental group participants had a higher proportion of allergic sensitization than participants who received placebo
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
0.5 to 10.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion
Hide Description 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.
Time Frame Three years (36 months) after Treatment Completion
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat minus one participant in placebo group who had a sibling in trial
Arm/Group Title OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Hide Arm/Group Description:
Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted 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. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Unit of Measure: participants
4 4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMIP With Timothy Grass, Cat and House Dust Mite Allergens, Placebo
Comments Participants who drop out (have missing efficacy endpoints) are considered treatment failures.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments Odds Ratios are calculated using unadjusted exact logistic regression with mid p-value to adjust for the discreteness of the distribution
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.2 to 6.1
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to First Onset of Asthma
Hide Description 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.
Time Frame From Treatment Initiation to Month 36 Status Post Treatment Completion
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat minus one participant in placebo group who had a sibling in trial
Arm/Group Title OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Hide Arm/Group Description:
Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted 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. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
Overall Number of Participants Analyzed 25 25
Mean (Standard Error)
Unit of Measure: Months
31.0  (1.9) 38.3  (2.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMIP With Timothy Grass, Cat and House Dust Mite Allergens, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments P-value is calculated using a log-rank test
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
0.6 to 5.6
Estimation Comments Hazard ratio and 95% confidence intervals are calculated using an unadjusted Cox regression
Time Frame Start of study through three years post-treatment (up to four years total)
Adverse Event Reporting Description This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
 
Arm/Group Title OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Hide Arm/Group Description Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted 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. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma. Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma.
All-Cause Mortality
OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/25 (32.00%)      7/26 (26.92%)    
Ear and labyrinth disorders     
Conductive deafness  1  0/25 (0.00%)  0 1/26 (3.85%)  1
Immune system disorders     
Anaphylactic reaction  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Infections and infestations     
Acute tonsillitis  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Ear infection  1  0/25 (0.00%)  0 2/26 (7.69%)  2
Gastroenteritis viral  1  0/25 (0.00%)  0 1/26 (3.85%)  1
Tonsillitis  1  1/25 (4.00%)  1 1/26 (3.85%)  1
Injury, poisoning and procedural complications     
Joint dislocation  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Skin laceration  1  0/25 (0.00%)  0 1/26 (3.85%)  1
Tooth fracture  1  0/25 (0.00%)  0 1/26 (3.85%)  1
Psychiatric disorders     
Breathing-related sleep disorder  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/25 (0.00%)  0 1/26 (3.85%)  2
Bronchial hyperreactivity  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Sleep apnoea syndrome  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Tonsillar hypertrophy  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Wheezing  1  0/25 (0.00%)  0 1/26 (3.85%)  1
Skin and subcutaneous tissue disorders     
Eczema  1  1/25 (4.00%)  1 0/26 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OMIP With Timothy Grass, Cat and House Dust Mite Allergens Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/25 (100.00%)      26/26 (100.00%)    
Blood and lymphatic system disorders     
Lymphadenopathy  1  1/25 (4.00%)  1 4/26 (15.38%)  4
Ear and labyrinth disorders     
Ear pain  1  1/25 (4.00%)  1 5/26 (19.23%)  6
Eye disorders     
Conjunctivitis  1  8/25 (32.00%)  23 14/26 (53.85%)  20
Conjunctivitis allergic  1  5/25 (20.00%)  5 3/26 (11.54%)  3
Eye pruritus  1  3/25 (12.00%)  4 5/26 (19.23%)  12
Lacrimation increased  1  6/25 (24.00%)  11 8/26 (30.77%)  18
Gastrointestinal disorders     
Abdominal discomfort  1  2/25 (8.00%)  3 1/26 (3.85%)  1
Abdominal pain upper  1  2/25 (8.00%)  3 1/26 (3.85%)  2
Constipation  1  4/25 (16.00%)  6 3/26 (11.54%)  3
Diarrhoea  1  17/25 (68.00%)  32 21/26 (80.77%)  57
Oral pruritus  1  2/25 (8.00%)  7 1/26 (3.85%)  1
Teething  1  8/25 (32.00%)  10 8/26 (30.77%)  22
Vomiting  1  15/25 (60.00%)  34 18/26 (69.23%)  52
General disorders     
Pyrexia  1  18/25 (72.00%)  60 19/26 (73.08%)  51
Immune system disorders     
Allergy to animal  1  2/25 (8.00%)  2 3/26 (11.54%)  11
Drug hypersensitivity  1  2/25 (8.00%)  2 1/26 (3.85%)  1
Food allergy  1  9/25 (36.00%)  35 8/26 (30.77%)  20
Hypersensitivity  1  7/25 (28.00%)  28 6/26 (23.08%)  14
Seasonal allergy  1  4/25 (16.00%)  12 4/26 (15.38%)  5
Infections and infestations     
Bronchitis  1  3/25 (12.00%)  3 1/26 (3.85%)  2
Croup infectious  1  1/25 (4.00%)  4 2/26 (7.69%)  2
Ear infection  1  10/25 (40.00%)  15 6/26 (23.08%)  17
Gastroenteritis  1  13/25 (52.00%)  30 12/26 (46.15%)  26
Lower respiratory tract infection  1  3/25 (12.00%)  9 4/26 (15.38%)  7
Nasopharyngitis  1  21/25 (84.00%)  141 23/26 (88.46%)  145
Otitis media  1  4/25 (16.00%)  14 3/26 (11.54%)  4
Otitis media acute  1  3/25 (12.00%)  5 4/26 (15.38%)  7
Pharyngitis  1  1/25 (4.00%)  1 3/26 (11.54%)  4
Respiratory tract infection viral  1  3/25 (12.00%)  4 2/26 (7.69%)  7
Rhinitis  1  7/25 (28.00%)  18 5/26 (19.23%)  9
Tonsillitis  1  7/25 (28.00%)  11 7/26 (26.92%)  17
Upper respiratory tract infection  1  22/25 (88.00%)  192 24/26 (92.31%)  184
Urinary tract infection  1  3/25 (12.00%)  5 3/26 (11.54%)  6
Varicella  1  2/25 (8.00%)  2 6/26 (23.08%)  6
Viral infection  1  12/25 (48.00%)  36 10/26 (38.46%)  26
Injury, poisoning and procedural complications     
Arthropod bite  1  4/25 (16.00%)  6 3/26 (11.54%)  5
Fall  1  4/25 (16.00%)  5 1/26 (3.85%)  1
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  2/25 (8.00%)  2 3/26 (11.54%)  3
Nervous system disorders     
Febrile convulsion  1  2/25 (8.00%)  5 1/26 (3.85%)  2
Headache  1  4/25 (16.00%)  5 4/26 (15.38%)  11
Respiratory, thoracic and mediastinal disorders     
Asthma  1  8/25 (32.00%)  25 4/26 (15.38%)  10
Cough  1  21/25 (84.00%)  111 20/26 (76.92%)  83
Epistaxis  1  3/25 (12.00%)  14 3/26 (11.54%)  8
Nasal congestion  1  11/25 (44.00%)  27 12/26 (46.15%)  48
Oropharyngeal pain  1  6/25 (24.00%)  11 2/26 (7.69%)  4
Rhinorrhoea  1  20/25 (80.00%)  82 20/26 (76.92%)  99
Sneezing  1  11/25 (44.00%)  33 8/26 (30.77%)  20
Stridor  1  2/25 (8.00%)  7 1/26 (3.85%)  1
Tonsillar hypertrophy  1  3/25 (12.00%)  4 2/26 (7.69%)  2
Wheezing  1  11/25 (44.00%)  62 10/26 (38.46%)  31
Skin and subcutaneous tissue disorders     
Dermatitis diaper  1  3/25 (12.00%)  4 0/26 (0.00%)  0
Eczema  1  11/25 (44.00%)  25 7/26 (26.92%)  12
Erythema  1  2/25 (8.00%)  2 1/26 (3.85%)  4
Pruritus  1  4/25 (16.00%)  12 2/26 (7.69%)  3
Rash  1  8/25 (32.00%)  20 6/26 (23.08%)  6
Urticaria  1  9/25 (36.00%)  28 6/26 (23.08%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
One participant in the placebo group could not be included in intent-to-treat analyses because a sibling was also in the study
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
Phone: 301-594-7669
EMail: DAITClinicalTrialsGov@niaid.nih.gov
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00346398    
Other Study ID Numbers: DAIT ITN025AD
First Submitted: June 27, 2006
First Posted: June 29, 2006
Results First Submitted: August 29, 2013
Results First Posted: December 16, 2013
Last Update Posted: May 1, 2017