Back to resultsAllergy Immunotherapy for the Reduction of Asthma (AIR)
Primary Purpose
Wheezing, Asthma, Allergy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allergen extracts (subcutaneous injections)
Standard of care
Sponsored by
About this trial
This is an interventional prevention trial for Wheezing focused on measuring Wheezing, Asthma, Allergy, Immunotherapy
Eligibility Criteria
Inclusion Criteria:
- Children between 18 months through 3 years who had at least 2 episodes of wheezing prior to enrolment.
- Positive skin tests or specific Immunoglobulin E (IgE) antibody titers to at least one of common airborne allergens: Dust Mite, cat, cockroach, mouse, dog, pollen (all allergy testing can be done at the screening visit at the study site).
The child must also fulfill the criteria for high risk of developing persistent asthma by meeting at least one of the following major conditions OR 2 of the following minor conditions:
- Major criteria: History of atopic dermatitis and/or parental history of asthma.
- Minor criteria: MD-diagnosed allergic rhinitis, wheezing unrelated to colds, blood eosinophils above 4%.
Exclusion Criteria:
- The child has a severe systemic condition (other than allergy or asthma) including (but not limited to) seizures, major congenital anomalies, physical and intellectual delay, cerebral palsy, chest surgery, tuberculosis, primary or secondary immunodeficiency or cardiac disorder (except a hemodynamically insignificant atrial or ventricular septum defect or heart murmur).
- The child was born following 35 or less weeks of gestation.
- Parental report that the child received oxygen for more than 5 days in the neonatal period, or required mechanical ventilation at any time since birth.
- The child fails to thrive, defined as crossing of two major growth percentile lines during the last year.
- The child has chronic lung disease of prematurity (CLDP), cystic fibrosis or any other chronic lung disease.
- The child ever received immunotherapy.
- The child ever received i.v. gammaglobulins or immunosuppressants (other than corticosteroids for asthma).
- History of a life-threatening asthma exacerbation which required intubation and mechanical ventilation.
Sites / Locations
- Jacobi Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
No immunotherapy, receive standard of care asthma treatment
Allergen immunotherapy
Arm Description
This group consists of children who do not receive allergy immunotherapy. Both groups - the experimental as well as the control group receive otherwise standard of care asthma and allergy treatment
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment
Outcomes
Primary Outcome Measures
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
The Asthma Severity Score is a customized score created for this study due to the lack of standardized instruments for this age group. It takes into account asthma symptom severity and frequency, as well as asthma medication dosing and potency. Data was collected at baseline and every 2 weeks through interviews conducted over the phone. If the caregiver could not be reached by the phone, the interview was conducted at the next face-to face opportunity (study or injection visit). The minimum score on this scale is 0 (no asthma symptoms and no asthma medicines used during the 14 day interview period). The maximum score is 224 (uncontrolled severe asthma with severe cough, shortness of breath and wheezing on 14 of 14 days, using Albuterol 2 puffs 4x/day, budesonide/formoterol 160ug/4.5ug 2 puffs twice daily and Montelukast 4mg daily on 14 of 14 days). Scores calculated from the collected data were averaged to produce one reported value at baseline and year 1, 2 and 3.
Secondary Outcome Measures
Number of Newly Gained Allergic Sensitizations as Assessed by Serum Specific Immunoglobulin E (IgE) Testing
Young children with allergies tend to develop additional environmental allergies over time. This study investigated if allergy immunotherapy could be used to prevent the development of new allergic sensitizations. Participants were tested for sensitivity to a panel of 8 common environmental allergens. Testing was conducted via serum specific immunoglobulin E (IgE) testing. A test was considered negative (non-allergic) if the specific IgE level was <0.35 kIU/L (Kilo International Units/Liter) and positive (allergic) if the levels was >0.35 kIU/L. A "test pair" is the result of a serum IgE test, for a specific allergen, done at two different times. Test pairs can be negative-negative, negative-positive (newly gained allergic sensitization), positive-negative (lost sensitization) or positive-positive. Reported values indicate the total number of newly gained allergic sensitization (negative-positive) for the group.
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
T regulatory cells are thought to play a role in mediating the effects of immunotherapy in increasing allergen tolerance and dampen the clinical expression of allergy. However, existing studies have not found clear relationship between numbers of T regulatory cells in blood and effect of immunotherapy. The aim of this analysis was to observe potential changes in T regulatory cell numbers in response to immunotherapy in this age group. Peripheral blood cells were acquired and analyzed for T regulatory (Treg) cell markers. In molecular biology, CD4+ (cluster of differentiation 4), a particular cell marker, is a glycoprotein found on the surface of immune cells such as T helper cells and certain groups of T regulatory cells. Testing was done at baseline and then every 12 months. Reported values represents the percentage of CD4+ that are Treg cells.
Incidence Rate of Systemic Corticosteroid Bursts (CSB) Per Child
Any reported use of consequent systemic corticosteroid use due to asthma exacerbation counted as one "corticosteroid burst" (CSB). For example, if a child used 5 days of prednisolone due to asthma exacerbation, this counted as one corticosteroid burst (CSB). An interval of at least 7 days was determined to be necessary to count 2 courses of systemic corticosteroids as separated bursts.
The presented data reflect the intention-to-treat analysis. The time between baseline and each participant's study end time was counted towards the "years in study". The incidence rate describes the number of CSB per child per "year in study".
Full Information
NCT ID
NCT01028560
First Posted
December 7, 2009
Last Updated
May 24, 2019
Sponsor
Albert Einstein College of Medicine
Collaborators
Jacobi Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01028560
Brief Title
Allergy Immunotherapy for the Reduction of Asthma
Acronym
AIR
Official Title
Efficacy of Allergy Immunotherapy in Preventing Asthma Morbidity in Atopic, Wheezing Children (Age 18 Months - 3 Years)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
October 2008 (Actual)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Albert Einstein College of Medicine
Collaborators
Jacobi Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this clinical study we aim to determine the effect of allergy immunotherapy in decreasing asthma and allergy related disease in children who had multiple episodes of wheezing and who are at high risk for developing persisting asthma. These risks include a history of asthma in the parents, allergies to environmental allergens (such as dust mite, cockroach or mouse) and other allergic diseases such as eczema or food allergies. Allergy Immunotherapy is not new and has been practiced for many years to treat asthma and environmental allergies in older children and adults, but has not yet been systematically studied in young children.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wheezing, Asthma, Allergy
Keywords
Wheezing, Asthma, Allergy, Immunotherapy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
No immunotherapy, receive standard of care asthma treatment
Arm Type
Active Comparator
Arm Description
This group consists of children who do not receive allergy immunotherapy. Both groups - the experimental as well as the control group receive otherwise standard of care asthma and allergy treatment
Arm Title
Allergen immunotherapy
Arm Type
Experimental
Arm Description
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment
Intervention Type
Biological
Intervention Name(s)
Allergen extracts (subcutaneous injections)
Intervention Description
Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-2 injections until a predetermined maintenance dose is reached. This maintenance dose varies by extract and accords to the general practice guidelines of immunotherapy. To increase safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase (year 2-3)
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
standard of care asthma and allergy treatment
Primary Outcome Measure Information:
Title
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
Description
The Asthma Severity Score is a customized score created for this study due to the lack of standardized instruments for this age group. It takes into account asthma symptom severity and frequency, as well as asthma medication dosing and potency. Data was collected at baseline and every 2 weeks through interviews conducted over the phone. If the caregiver could not be reached by the phone, the interview was conducted at the next face-to face opportunity (study or injection visit). The minimum score on this scale is 0 (no asthma symptoms and no asthma medicines used during the 14 day interview period). The maximum score is 224 (uncontrolled severe asthma with severe cough, shortness of breath and wheezing on 14 of 14 days, using Albuterol 2 puffs 4x/day, budesonide/formoterol 160ug/4.5ug 2 puffs twice daily and Montelukast 4mg daily on 14 of 14 days). Scores calculated from the collected data were averaged to produce one reported value at baseline and year 1, 2 and 3.
Time Frame
baseline and every two weeks up to end of study (up to 36 months)
Secondary Outcome Measure Information:
Title
Number of Newly Gained Allergic Sensitizations as Assessed by Serum Specific Immunoglobulin E (IgE) Testing
Description
Young children with allergies tend to develop additional environmental allergies over time. This study investigated if allergy immunotherapy could be used to prevent the development of new allergic sensitizations. Participants were tested for sensitivity to a panel of 8 common environmental allergens. Testing was conducted via serum specific immunoglobulin E (IgE) testing. A test was considered negative (non-allergic) if the specific IgE level was <0.35 kIU/L (Kilo International Units/Liter) and positive (allergic) if the levels was >0.35 kIU/L. A "test pair" is the result of a serum IgE test, for a specific allergen, done at two different times. Test pairs can be negative-negative, negative-positive (newly gained allergic sensitization), positive-negative (lost sensitization) or positive-positive. Reported values indicate the total number of newly gained allergic sensitization (negative-positive) for the group.
Time Frame
Baseline and end of treatment (36 months)
Title
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
Description
T regulatory cells are thought to play a role in mediating the effects of immunotherapy in increasing allergen tolerance and dampen the clinical expression of allergy. However, existing studies have not found clear relationship between numbers of T regulatory cells in blood and effect of immunotherapy. The aim of this analysis was to observe potential changes in T regulatory cell numbers in response to immunotherapy in this age group. Peripheral blood cells were acquired and analyzed for T regulatory (Treg) cell markers. In molecular biology, CD4+ (cluster of differentiation 4), a particular cell marker, is a glycoprotein found on the surface of immune cells such as T helper cells and certain groups of T regulatory cells. Testing was done at baseline and then every 12 months. Reported values represents the percentage of CD4+ that are Treg cells.
Time Frame
Baseline and every 12 months until end of treatment (36 months)
Title
Incidence Rate of Systemic Corticosteroid Bursts (CSB) Per Child
Description
Any reported use of consequent systemic corticosteroid use due to asthma exacerbation counted as one "corticosteroid burst" (CSB). For example, if a child used 5 days of prednisolone due to asthma exacerbation, this counted as one corticosteroid burst (CSB). An interval of at least 7 days was determined to be necessary to count 2 courses of systemic corticosteroids as separated bursts.
The presented data reflect the intention-to-treat analysis. The time between baseline and each participant's study end time was counted towards the "years in study". The incidence rate describes the number of CSB per child per "year in study".
Time Frame
From baseline through end of study (maximum 36 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Children between 18 months through 3 years who had at least 2 episodes of wheezing prior to enrolment.
Positive skin tests or specific Immunoglobulin E (IgE) antibody titers to at least one of common airborne allergens: Dust Mite, cat, cockroach, mouse, dog, pollen (all allergy testing can be done at the screening visit at the study site).
The child must also fulfill the criteria for high risk of developing persistent asthma by meeting at least one of the following major conditions OR 2 of the following minor conditions:
Major criteria: History of atopic dermatitis and/or parental history of asthma.
Minor criteria: MD-diagnosed allergic rhinitis, wheezing unrelated to colds, blood eosinophils above 4%.
Exclusion Criteria:
The child has a severe systemic condition (other than allergy or asthma) including (but not limited to) seizures, major congenital anomalies, physical and intellectual delay, cerebral palsy, chest surgery, tuberculosis, primary or secondary immunodeficiency or cardiac disorder (except a hemodynamically insignificant atrial or ventricular septum defect or heart murmur).
The child was born following 35 or less weeks of gestation.
Parental report that the child received oxygen for more than 5 days in the neonatal period, or required mechanical ventilation at any time since birth.
The child fails to thrive, defined as crossing of two major growth percentile lines during the last year.
The child has chronic lung disease of prematurity (CLDP), cystic fibrosis or any other chronic lung disease.
The child ever received immunotherapy.
The child ever received i.v. gammaglobulins or immunosuppressants (other than corticosteroids for asthma).
History of a life-threatening asthma exacerbation which required intubation and mechanical ventilation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriele de Vos, M.D., M.Sc.
Organizational Affiliation
Einstein, Jacobi Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jacobi Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
14583928
Citation
Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2003;(4):CD001186. doi: 10.1002/14651858.CD001186.
Results Reference
background
PubMed Identifier
16461125
Citation
Roberts G, Hurley C, Turcanu V, Lack G. Grass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma. J Allergy Clin Immunol. 2006 Feb;117(2):263-8. doi: 10.1016/j.jaci.2005.09.054.
Results Reference
background
PubMed Identifier
12169173
Citation
Pifferi M, Baldini G, Marrazzini G, Baldini M, Ragazzo V, Pietrobelli A, Boner AL. Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study. Allergy. 2002 Sep;57(9):785-90. doi: 10.1034/j.1398-9995.2002.23498.x.
Results Reference
background
PubMed Identifier
33418053
Citation
de Vos G, Viswanathan S, Pichardo Y, Nazari R, Jorge Y, Ren Z, Serebrisky D, Rosenstreich D, Wiznia A. A randomized trial of subcutaneous allergy immunotherapy in inner-city children with asthma less than 4 years of age. Ann Allergy Asthma Immunol. 2021 Apr;126(4):367-377.e5. doi: 10.1016/j.anai.2020.12.016. Epub 2021 Jan 6.
Results Reference
derived
PubMed Identifier
23706713
Citation
de Vos G, Nazari R, Ferastraoaru D, Parikh P, Geliebter R, Pichardo Y, Wiznia A, Rosenstreich D. Discordance between aeroallergen specific serum IgE and skin testing in children younger than 4 years. Ann Allergy Asthma Immunol. 2013 Jun;110(6):438-43. doi: 10.1016/j.anai.2013.03.006. Epub 2013 Apr 11.
Results Reference
derived
PubMed Identifier
23176889
Citation
de Vos G, Shankar V, Nazari R, Kooragayalu S, Smith M, Wiznia A, Rosenstreich D. Fear of repeated injections in children younger than 4 years receiving subcutaneous allergy immunotherapy. Ann Allergy Asthma Immunol. 2012 Dec;109(6):465-9. doi: 10.1016/j.anai.2012.10.003. Erratum In: Ann Allergy Asthma Immunol. 2013 Mar;110(3):216.
Results Reference
derived
Learn more about this trial
Allergy Immunotherapy for the Reduction of Asthma
We'll reach out to this number within 24 hrs