- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03784781
Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma (CLASSE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Severe asthma of the child is characterized by chronic eosinophilic infiltration of the bronchial mucosa associated with bronchial remodeling.
The mechanisms responsible for these phenomena are still misunderstood. Animal models suggest that type 2 innate lymphoid cells (ILC2) may be responsible for inflammation and bronchial remodeling in asthma. In mice, ILC2 stimulated by the pulmonary epithelium by viral aggression or allergenic exposure release cytokines of the TH2 type such as IL-5 and IL-13 and amphiregulin, involved in the recruitment and differentiation of eosinophils, bronchoconstriction, mucus secretion and the restoration of epithelial integrity.
In humans, ILC2 would be more abundant in the bronchoalveolar lavage (BAL) and peripheral blood of asthmatic patients compared to control subjects. However, the presence of ILC2 in the bronchial mucosa of asthmatic patients has never been identified.
The hypothesis tested is that ILC2 are more abundant in bronchial mucosa, BAL, and blood in children with severe asthma than in non-asthmatics. The results of this study would improve the knowledge of the mechanisms responsible for bronchial inflammation in asthma, consider therapies to prevent its development and modify the natural history of the disease.
The main objectives of this study are to show that the number of ILC2 in bronchial mucosa and BAL is higher in asthmatic children than in non-asthmatics, that the number of ILC2 in the bronchial mucosa and BAL is correlated with the number of eosinophils in bronchial mucosa and BAL, to determine whether the number of ILC2 in lungs correlate with asthma symptoms, and to determine whether there is a correlation between plasma and bronchial ILC2.
Bronchoscopy with BAL and bronchial mucosal biopsies will be performed in 20 children with severe asthma and 20 control subjects in the department of pediatric pulmonology and allergy of Necker Hospital.
ILC2 will be identified in the BAL, in the bronchial mucosa and peripheral blood by flow cytometry. The median values of the number of ILC2 will be compared between asthmatic and non-asthmatic patients by the Mann-Whitney non-parametric test. The correlations will be established by the Spearman rank test. A value of p < 0.05 will be considered significant.
Study Type
Contacts and Locations
Study Locations
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Paris, France, 75015
- Hôpital Necker Enfants Malades
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Controls :
- Minors aged 6 to 18 matched in age with severe asthmatic children
- Non-asthmatic children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
- To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection
Severe asthmatic children :
- Minors aged 6 to 18
- Children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
- To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection
- Severe uncontrolled asthma is defined by the need to maintain a treatment with high doses of inhaled corticosteroids and a long-acting bronchodilator (B2LDA) and/or an anti-leukotriene
Exclusion Criteria:
- Children with an immune deficiency, will be excluded
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Asthmatic children
Severe uncontrolled asthma is defined by the need to maintain a treatment with high doses of inhaled corticosteroids and a long-acting bronchodilator (B2LDA) and/or an anti-leukotriene
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Mucosal biopsies under general anesthesia of the segmental bronchi of the right or left lower lobe
Blood collection (+15mL/ current care)
Bronchoalveolar lavage fluid (3mL/Kg)
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Controls
Non-asthmatic children, paired in age, requiring bronchial endoscopy with BAL and bronchial mucosa biopsy.
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Mucosal biopsies under general anesthesia of the segmental bronchi of the right or left lower lobe
Blood collection (+15mL/ current care)
Bronchoalveolar lavage fluid (3mL/Kg)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of type 2 innate lymphoid cells
Time Frame: Day 0
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Type 2 innate lymphoid cells
|
Day 0
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Eosinophils
Time Frame: Day 0
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Eosinophils
|
Day 0
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Airway remodeling: reticular basement membrane thickness
Time Frame: Day 0
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Reticular basement membrane thickness will be expressed in µm.
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Day 0
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Airway remodeling: airway smooth muscle area
Time Frame: Day 0
|
The percentage of the submucosa occupied by airway smooth muscle will be determined on hematoxylin-eosin-stained and anti-airway smooth muscle antibody treated sections, respectively.
The bundles of airway smooth muscle will be enclosed by a line and the area they occupied will be calculated by image analysis.
The airway smooth muscle area will be expressed as the percentage of surface of the submucosa occupied by airway smooth muscle.
|
Day 0
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Airway remodeling: epithelial integrity
Time Frame: Day 0
|
Epithelial integrity will be defined as the percentage of the total length of epithelium that will be intact.
|
Day 0
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Airway remodeling: vessel number
Time Frame: Day 0
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The number of vessels stained with anti-CD31 mAb will be determined from at least one grid (0.1 mm2) per biopsy, and reported as the median number of positive sections per 0.1 mm2.
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Day 0
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Airway remodeling: mucus gland area
Time Frame: Day 0
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The percentage of the submucosa occupied by mucus gland will be determined on hematoxylin-eosin-stained and anti-airway smooth muscle antibody treated sections, respectively.
The mucus glands will be enclosed by a line and the area occupied will be calculated by image analysis.
The mucus gland area will be expressed as the percentage of surface of the submucosa occupied by mucus gland.
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Day 0
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Airway inflammation: bronchoalveolar lavage (BAL)
Time Frame: Day 0
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BAL fluid will be assed for inflammation
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Day 0
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Airway inflammation: bronchial mucosa
Time Frame: Day 0
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Bronchial sections will be stained with May-Grunwald-Giemsa.The number of inflammatory cells will be assessed in the submucosa and expressed as the number of cells per square millimeters of submucosal area.
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Day 0
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Inflammation in blood
Time Frame: Day 0
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Day 0
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Metabolomic signature
Time Frame: Day 0
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Non-targeted metabolomics analysis will be performed on plasma.
Metabolic profiles will be obtained using two complementary LC-MS methods, to identify metabolites discriminating different patients.
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Day 0
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Microbiota analysis
Time Frame: Day 0
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Microbiota analysis will be performed on BAL using PCR ARN 16S.
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Day 0
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP180357
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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