AsthmaNAIL-5NCT02866487
Lung Fluid and Peripheral Blood Neutrophil IL-5 Surface Receptor in Children With Asthma
An observational study of Asthma, run by University of Virginia at 1 site in United States.
Trial summary
The pattern of lower airway inflammation in asthma is heterogeneous, but in many patients, the polymorphonuclear neutrophil (PMN) is the predominant granulocyte infiltrating the airspaces. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Asthma
- What is being tested?
- Bronchoscopy
- Type of treatment
- Surgery or procedure
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to 14 May 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: The study population includes children with refractory respiratory symptoms, most who will have poorly-controlled asthma. An age similar comparison group with structural lung anomalies who undergo diagnostic bronchoscopy will serve as controls.
Who may be able to join
- Ages 0-17
- Treatment-resistant, refractory respiratory symptoms
- Scheduled for a clinical diagnostic bronchoscopy
Who cannot join
- Known lower respiratory tract infection within 60 days of scheduled bronchoscopy
- Systemic disorders involving the heart, respiratory system, CNS, renal, and endocrine systems
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Health System
Charlottesville, Virginia, 22908
About this study
The pattern of lower airway inflammation in asthma is heterogeneous, but in many patients, the polymorphonuclear neutrophil (PMN) is the predominant granulocyte infiltrating the airspaces. Although it is known to have an important function in innate immune defense, the role of the PMN in asthma has not been well elucidated. In work in progress, the investigators have identified the receptor for IL-5 on the surface of bronchoalveolar lavage (BAL) PMNs in a subset of children with severe, treatment-resistant asthma, a characteristic that is not found in peripheral blood neutrophils. While the function of this IL-5 receptor has yet to be determined, preliminary evidence strongly supports a mechanism linking neutrophilic with type 2 inflammation in the lower airways of children with asthma, a discovery that has exciting potential to modify the treatment of asthma.
The primary objective of this observational cross-sectional study is to test the overall hypothesis that therapeutic intervention directed against the IL-5R on lung PMNs will decrease inflammation and improve clinical outcomes in patients with poorly controlled asthma. The secondary study objective is to demonstrate that IL-5R expression on lung-infiltrating PMNs is functional, will activate known IL-5R-induced signaling pathways, and will lead to enhanced PMN pro-inflammatory activity including increased PMN recruitment, prolonged survival, degranulation, and release of reactive oxygen species.
- Conditions
- Asthma
- Being tested
- Bronchoscopy
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BronchoscopyProcedure or surgery
A diagnostic bronchoscopy will be conducted for clinical indications in children referred to the University of Virginia Children's Hospital for evaluation of respiratory symptoms
| Study group | Role | What they receive |
|---|---|---|
| Asthmatics | 0-5 years of age: Intermittent cough, wheeze, chest symptoms AND one or more of the following: Eczema Eosinophilia Elevated total IgE Positive family history
6-17 years of age: Physician diagnosis Current treatment with one or more asthma medications Recurrent episodes of cough, wheeze, chest discomfort, pain Receives: Procedure: Bronchoscopy | |
| Age-Similar Non-asthmatic Controls | Age-similar controls will undergo diagnostic bronchoscopy for clinical indications in the absence of known asthma, including recurrent pneumonia, congenital lung anomalies, prolonged cough, suspected laryngeal abnormalities, and suspected aspiration syndromes. Inclusion in the final set to be determined post-procedure based on BAL granulocyte profiles. To be included as a control, participants must have pauci-granular BAL counts (less than 2 percent eosinophils and less than 4 percent PMN), no positive allergen sensitization, and no positive viral or bacterial studies from analysis of BAL fluid. Receives: Procedure: Bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent neutrophils bearing surface markers for IL-5 Receptor
The percentage of neutrophils which bear surface markers for the IL5-R in lung fluid and peripheral blood will be compared in children with different asthma phenotypes
Measured: 6+ months post bronchoscopy
Secondary outcomes (4)
In vitro analysis of IL-5 Receptor (IL-5 R) function: Signaling via the IL-5 R displayed on neutrophils from the BAL (and if necessary, peripheral blood) following ligand (IL-5) binding
This measure will assess the phosphorylation of STAT 5 and simultaneously phosphorylation of AKT (as a surrogate for activation of PI 3 kinase) following treatment of neutrophils with IL-5 (i.e. IL-5 R engagement). Engagement of the GM-CSF receptor on the neutrophils by its ligand will serve as a control for the capacity of neutrophils to undergo signal transduction in response to ligands. Additional control will be activation (phosphorylation) of STAT 5 on eosinophils responding to IL-5 (i.e IL-5 R engagement). This analysis will be carried out using flow cytometry to evaluate phosphorylation of the indicated signaling intermediates. This analysis will establish whether the IL-5 R on BAL neutrophils is functional (i.e. capable of transducing a signal following ligand binding).
Measured: 48-72 hours post bronchoscopy
Measurement of neutrophil degranulation and inflammatory mediator production following IL-5 binding to its receptor on neutrophils isolated from the BAL
Neutrophil activation will assess the production of specific cytokines (e.g. TNFa) and chemokines (e.g. CXCL 10) as well as release of granule contents (e.g. lysozyme and proteases) following IL-5 R engagement. These functions will be assessed by ELISA. Analysis of this parameter will elucidate whether signaling through the IL-5 R results in classical activation of IL-5 R positive neutrophils, the result of which is enhanced injury and inflammation.
Measured: 48-72 hours post bronchoscopy
Production of Reactive Oxygen Species following IL-5 R engagement
Reactive Oxygen Species will evaluate the generation of ROS by neutrophils following IL-5 R engagement in BAL neutrophils (and if appropriate neutrophils isolated from peripheral blood). This analysis will be carried out using colorimetric analysis of color change in neutrophils exposed to ROS sensitive dye. This analysis will determine if exposure to IL-5 results in ROS production by neutrophils and as a consequence the potential for increased tissue damage to the lungs.
Measured: 48-72 hours post bronchoscopy
Measurement of neutrophil survival in culture upon IL-5 R engagement in vitro
Neutrophil survival will analyze the survival in culture of neutrophils isolated from the BAL following exposure to IL-5 in vitro. Apoptosis of neutrophils over time in culture will be evaluated by flow cytometry. This analysis will determine whether exposure of lung neutrophils to IL-5 will enhance their survival and therefore the potential of neutrophils activated in response to IL-5 to promote enhanced inflammation and injury.
Measured: 48-72 hours post bronchoscopy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2016 (estimated)
- Study startAug 2016
- Primary completion14 May 2018
- Study completion14 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Willliam Gerald Teague, University of Virginia
- Investigators
- William G Teague, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02866487
- Sponsor's protocol ID
- NAIL-5
- Acronym
- NAIL-5
- Status last verified
- Feb 2022
- First submitted
- 28 Jul 2016
- Last updated
- 7 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Fluid and Peripheral Blood Neutrophil IL-5 Surface Receptor in Children With Asthma
- ClinicalTrials.gov ID
- NCT02866487
- Acronym / sponsor ID
- NAIL-5 / NAIL-5
- Conditions
- Asthma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- 14 May 2018 (actual)
- Study completion
- 14 May 2018 (actual)
- First posted
- 15 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The pattern of lower airway inflammation in asthma is heterogeneous, but in many patients, the polymorphonuclear neutrophil (PMN) is the predominant granulocyte infiltrating the airspaces. Although it is known to have an important function in innate immune defense, the role of the PMN in asthma has not been well elucidated. In work in progress, the investigators have identified the receptor for IL-5 on the surface of bronchoalveolar lavage (BAL) PMNs in a subset of children with severe, treatment-resistant asthma, a characteristic that is not found in peripheral blood neutrophils. While the function of this IL-5 receptor has yet to be determined, preliminary evidence strongly supports a mechanism linking neutrophilic with type 2 inflammation in the lower airways of children with asthma, a discovery that has exciting potential to modify the treatment of asthma.
The primary objective of this observational cross-sectional study is to test the overall hypothesis that therapeutic intervention directed against the IL-5R on lung PMNs will decrease inflammation and improve clinical outcomes in patients with poorly controlled asthma. The secondary study objective is to demonstrate that IL-5R expression on lung-infiltrating PMNs is functional, will activate known IL-5R-induced signaling pathways, and will lead to enhanced PMN pro-inflammatory activity including increased PMN recruitment, prolonged survival, degranulation, and release of reactive oxygen species.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Asthmatics | – | Procedure: Bronchoscopy0-5 years of age: Intermittent cough, wheeze, chest symptoms AND one or more of the following: Eczema Eosinophilia Elevated total IgE Positive family history 6-17 years of age: Physician diagnosis Current treatment with one or more asthma medications Recurrent episodes of cough, wheeze, chest discomfort, pain |
| Age-Similar Non-asthmatic Controls | – | Procedure: BronchoscopyAge-similar controls will undergo diagnostic bronchoscopy for clinical indications in the absence of known asthma, including recurrent pneumonia, congenital lung anomalies, prolonged cough, suspected laryngeal abnormalities, and suspected aspiration syndromes. Inclusion in the final set to be determined post-procedure based on BAL granulocyte profiles. To be included as a control, participants must have pauci-granular BAL counts (less than 2 percent eosinophils and less than 4 percent PMN), no positive allergen sensitization, and no positive viral or bacterial studies from analysis of BAL fluid. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study population includes children with refractory respiratory symptoms, most who will have poorly-controlled asthma. An age similar comparison group with structural lung anomalies who undergo diagnostic bronchoscopy will serve as controls.
Key inclusion criteria (3 listed)
- Ages 0-17
- Treatment-resistant, refractory respiratory symptoms
- Scheduled for a clinical diagnostic bronchoscopy
Key exclusion criteria (2 listed)
- Known lower respiratory tract infection within 60 days of scheduled bronchoscopy
- Systemic disorders involving the heart, respiratory system, CNS, renal, and endocrine systems
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 |
|---|---|---|
| BronchoscopyA diagnostic bronchoscopy will be conducted for clinical indications in children referred to the University of Virginia Children's Hospital for evaluation of respiratory symptoms | Procedure or surgery | Age-Similar Non-asthmatic Controls, Asthmatics |
Primary outcome
Percent neutrophils bearing surface markers for IL-5 Receptor
Time frame: 6+ months post bronchoscopy
The percentage of neutrophils which bear surface markers for the IL5-R in lung fluid and peripheral blood will be compared in children with different asthma phenotypes
4 secondary outcomes
In vitro analysis of IL-5 Receptor (IL-5 R) function: Signaling via the IL-5 R displayed on neutrophils from the BAL (and if necessary, peripheral blood) following ligand (IL-5) binding
Time frame: 48-72 hours post bronchoscopy
Measurement of neutrophil degranulation and inflammatory mediator production following IL-5 binding to its receptor on neutrophils isolated from the BAL
Time frame: 48-72 hours post bronchoscopy
Production of Reactive Oxygen Species following IL-5 R engagement
Time frame: 48-72 hours post bronchoscopy
Measurement of neutrophil survival in culture upon IL-5 R engagement in vitro
Time frame: 48-72 hours post bronchoscopy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2022.
- Individual participant dataSharing planned: No
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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.
William G Teague, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma, run by University of Virginia 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 3 inclusion and 2 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 7 Feb 2022. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percent neutrophils bearing surface markers for IL-5 Receptor (time frame: 6+ months post bronchoscopy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Feb 2022; AzTrials last refreshed its copy on 6 Nov 2026.