Effect of Benralizumab on Airway Remodeling in Asthma

NCT04365205 | Recruiting

• 1 other identifier: CHUBX 2019/34
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The anti-interleukin (IL)-5 receptor benralizumab inhibits eosinophilic inflammation but its potential effect on airway remodeling remains unknown. The main objective of this study is to assess the effect of benralizumab in an in vitro model of airway remodeling using cells obtained from asthmatic patients.

Conditions

Asthma

Keywords

Asthma; remodeling; IL-5 receptor; smooth muscle; biotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Bronchial smooth muscle (BSM) cells obtained from severe asthmatics measured in vitro using BrdU incorporation.

  Determine the proliferation of BSM cells obtained from severe asthmatics measured in vitro using BrdU incorporation.

  Month 12

Secondary Outcomes (10)

• Number of cultured BSM cell from non-severe asthmatics and healthy volunteers measured using BrdU incorporation.

  Month 12

• Number of different genes

  Month 12

• Measure the inflammatory mediators and extracellular components

  Month 12

• Measure the fluorescence intensity of IL-5 receptor subunit alpha on BSM cells

  Month 12

• Count the number of mitochondria / BSM area (x107/mm2)

  Month 12

Study Arms (3)

severe asthma

* Diagnosis of severe asthma according to the American Thoracic Society / European Respiratory Society task force. * Documented post-bronchodilator reversibility of at least 12% and at least 200 mL in Forced expiratory volume forced expiratory volume at one second (FEV1) within 12 months before enrollment. * Documented blood eosinophils ≥ 300 cells per μL within 12 months or blood eosinophils ≥150 cells per μL at visit 1.

Procedure: Endobronchial biopsy

non-severe asthma

• Diagnosis of non-severe asthma according to the Global Initiative for Asthma (GINA).

Procedure: Endobronchial biopsy

non-asthmatic controls

* No prior history of any chronic respiratory disease including asthma. * No prior history of allergy, i.e. allergic rhinitis, allergic conjunctivitis, hay fever, eczema. * No clinically significant abnormalities as determined by medical history, measurement of vital signs, physical examination, hematologic assessments and ECG at visit 1. * Normal lung function with FEV1 \> 90%.

Procedure: Endobronchial biopsy

Interventions

Endobronchial biopsy PROCEDURE

Endobronchial biopsies will be collected following a standardized procedure based on established guidelines. Before the procedure, asthmatic subjects will receive 400 μg of salbutamol with the aid of an aerosol chamber to open up the airways before the procedure. Anesthesia of the upper airways will be achieved with lidocaine 5% spray. The total amount of lidocaine per subject is limited to 225 mg. General anesthesia will be obtained using propofol (average dose of 1.5 to 2 mg/kg). The fiberoptic bronchoscope (Pentax BF 15V, Argenteuil, France) is introduced and 8 to 10 biopsies will be taken from the middle lobe and the lower right lobe. Standard procedures such as bronchial brushing and bronchial fluid aspiration will also be performed. The duration of bronchoscopy is 15 minutes to 30 minutes. After the procedures, subjects will receive a short acting bronchodilator if required.

non-asthmatic controls; non-severe asthma; severe asthma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy subjects with no prior history of any chronic respiratory disease including asthma (n = 20), non-severe asthmatics subjects (n = 20) and severe asthmatics (n = 20).

You may qualify if:

• Healthy subjects
• Written informed consent indicating that they understand the purpose and procedures required for the study and are willing to participate in the study.
• Age higher than 18 years.
• No prior history of any chronic respiratory disease including asthma.
• No prior history of allergy, i.e. allergic rhinitis, allergic conjunctivitis, hay fever, eczema.
• No clinically significant abnormalities as determined by medical history, measurement of vital signs, physical examination, hematologic assessments and ECG at visit 1.
• Normal lung function with FEV1 \> 90%.
• Non-severe asthmatics subjects
• Written informed consent indicating that they understand the purpose and procedures required for the study and are willing to participate in the study.
• Age higher than 18 years.
• Diagnosis of non-severe asthma according to the Global Initiative for Asthma (GINA), i.e. GINA steps 1, 2 or 3 (18).
• Documented post-bronchodilator reversibility of at least 12% and at least 200 mL in FEV1 within 12 months before enrolment, or PC20 methacholine \< 16 mg/mL documented within 12 months prior to screening.
• Documented blood eosinophils ≥300 cells per μL within 12 months or blood eosinophils ≥150 cells per μL at visit 1.
• Severe asthmatics subjects
• Written inform consent indicating that they understand the purpose and procedures required for the study and are willing to participate in the study.

You may not qualify if:

• Active smoker or former smoker.
• Diagnosis of chronic obstructive pulmonary disease (COPD), cystic fibrosis, or other significant respiratory disorder including significant occupational or environmental exposures with ongoing respiratory symptoms.
• CT scan abnormality related to any respiratory disease other than asthma.
• Recent asthma exacerbation (less than 6 weeks before bronchoscopy).
• Contraindications related to bronchoscopy:
• coagulation disorders,
• unstable cardiovascular conditions,
• FEV1 lower than 1 litter,
• a fasting state of less than 6 hours for food and less than 2 hours for drink.
• Contraindications to general anesthesia or medications (for propofol: hypersensitivity to the active substance and to any of the excipients; for lidocaine: hypersensitivity to the active substance and to any of the excipients or to local anesthetics of the amide type, epilepsy, porphyria) used in the bronchoscopy procedure.
• Contraindications related to MRI:
• Pacemaker or implantable cardioverter defibrillator
• Metallic foreign body in the eye
• Cerebral aneurysm clips
• Insulin pumps

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CIC-P - Centre François Magendie - G3 - Hôpital Haut-Lévêque

Bordeaux, 33604, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bronchial specimens

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Pierre-Olivier GIRODET, MD, PhD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pierre-Olivier GIRODET, MD, PhD

CONTACT

+33 5 57 62 31 94; pierre-olivier.girodet@u-bordeaux.fr

Karelle FOREST

CONTACT

+33 5 57 62 31 94; Karelle.FOREST@u-bordeaux.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 28, 2020
• Study Start: September 23, 2020
• Primary Completion: October 5, 2024
• Study Completion: October 5, 2024
• Last Updated: February 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)