WheezingPhase 1/2AIRNCT01028560
Allergy Immunotherapy for the Reduction of Asthma
A Phase 1/2 study testing Allergen extracts (subcutaneous injections) in people with Wheezing and Asthma, run by Albert Einstein College of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 months to 3 years
- What is being tested?
- Allergen extracts (subcutaneous injections)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Apr 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months to 3 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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%.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Allergy Immunotherapy in Preventing Asthma Morbidity in Atopic, Wheezing Children (Age 18 Months - 3 Years)
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.
- Being tested
- Allergen extracts (subcutaneous injections), Standard of care
- Keywords
- Wheezing, Asthma, Allergy, Immunotherapy
- Medical subject headings
- Respiratory Sounds, Asthma, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allergen extracts (subcutaneous injections)Biological
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)
Standard of careOther
standard of care asthma and allergy treatment
| Study group | Role | What they receive |
|---|---|---|
| No immunotherapy, receive standard of care asthma treatment | Active comparator | 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 Receives: Other: Standard of care |
| Allergen immunotherapy | Experimental | 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 Receives: Biological: Allergen extracts (subcutaneous injections); Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline and every two weeks up to end of study (up to 36 months)
Secondary outcomes (3)
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.
Measured: Baseline and end of treatment (36 months)
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.
Measured: Baseline and every 12 months until end of treatment (36 months)
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".
Measured: From baseline through end of study (maximum 36 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
- Study startOct 2008
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for WheezingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Jacobi Medical Center
- Responsible party
- Principal investigator, Gabriele de Vos, Albert Einstein College of Medicine
- Investigators
- Gabriele de Vos, M.D., M.Sc., Principal investigator, Einstein, Jacobi Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01028560
- Sponsor's protocol ID
- 2007-280
- Acronym
- AIR
- Status last verified
- Apr 2019
- First submitted
- 7 Dec 2009
- Last updated
- 28 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2003;(4):CD001186. doi: 10.1002/14651858.CD001186.
PubMed 14583928Roberts 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.
PubMed 16461125Pifferi 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.
PubMed 12169173de 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.
PubMed 33418053de 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.
PubMed 23706713de 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.
PubMed 23176889
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Allergy Immunotherapy in Preventing Asthma Morbidity in Atopic, Wheezing Children (Age 18 Months - 3 Years)
- ClinicalTrials.gov ID
- NCT01028560
- Acronym / sponsor ID
- AIR / 2007-280
- Keywords
- Wheezing, Asthma, Allergy, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Collaborators
- Jacobi Medical Center
- Study start
- Oct 2008 (actual)
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 9 Dec 2009 (estimated)
- Results
- Posted 28 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No immunotherapy, receive standard of care asthma treatment | Active comparator | Other: Standard of careThis 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 |
| Allergen immunotherapy | Experimental | Biological: Allergen extracts (subcutaneous injections), Other: Standard of careThis 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 |
Who may qualify
- Ages
- 18 months to 3 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allergen extracts (subcutaneous injections)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) | Biological | Allergen immunotherapy |
| Standard of carestandard of care asthma and allergy treatment | Other | Allergen immunotherapy, No immunotherapy, receive standard of care asthma treatment |
Primary outcome
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
Time frame: baseline and every two weeks up to end of study (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.
3 secondary outcomes
Number of Newly Gained Allergic Sensitizations as Assessed by Serum Specific Immunoglobulin E (IgE) Testing
Time frame: Baseline and end of treatment (36 months)
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
Time frame: Baseline and every 12 months until end of treatment (36 months)
Incidence Rate of Systemic Corticosteroid Bursts (CSB) Per Child
Time frame: From baseline through end of study (maximum 36 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14583928Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2003;(4):CD001186. doi: 10.1002/14651858.CD001186.
- Background: PubMed 16461125Roberts 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.
- Background: PubMed 12169173Pifferi 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.
- Derived from this study: PubMed 33418053de 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.
- Derived from this study: PubMed 23706713de 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.
- Derived from this study: PubMed 23176889de 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriele de Vos, M.D., M.Sc. principal investigator
Einstein, Jacobi Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allergen extracts (subcutaneous injections) in people with Wheezing and Asthma, run by Albert Einstein College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months) (time frame: baseline and every two weeks up to end of study (up to 36 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01028560, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2019.