AsthmaBENRAMODNCT04365205
Effect of Benralizumab on Airway Remodeling in Asthma
An observational study of Asthma, run by University Hospital, Bordeaux at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- Endobronchial biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 23 Sep 2020to 5 Oct 2024
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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).
Who may be able to join
- 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.
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- 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.
- Age higher than 18 years.
- Diagnosis of severe asthma according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) task force (19).
- Documented post-bronchodilator reversibility of at least 12% and at least 200 mL in FEV1 within 12 months before enrolment.
- Documented blood eosinophils ≥300 cells per μL within 12 months or blood eosinophils ≥150 cells per μL at visit 1.
Who cannot join
- 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,
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- 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
- Claustrophobia
- Positive urinary pregnancy test at screening for women of child-bearing potential
- Breastfeeding woman.
- Previously received benralizumab.
- History of any clinically significant medical illness or medical disorders including (but not limited to) cardiovascular disease, neuromuscular, hematological disease including bleeding disorders, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
- Recent history (within previous 6 months) of alcohol or drug abuse.
- Persons placed under judicial protection.
- Persons participating in another research including a period of exclusion still in course.
- Severely altered physical and/or psychological health which, according to, the investigator, could affect the participant's compliance of the study.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CIC-P - Centre François Magendie - G3 - Hôpital Haut-Lévêque
Bordeaux, 33604
Pierre-Olivier GIRODET, MD, PhD, (0)5 57 62 31 94 ext. +33, pierre-olivier.girodet@chu-bordeaux.fr
Karelle FOREST, (0)5 57 62 31 94 ext. +33, Karelle.FOREST@u-bordeaux.fr
About this study
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.
Read the detailed description
Sixty subjects will be recruited: 20 patients with severe asthma patients, 20 patients with non-severe asthma and 20 non-asthmatic controls. Inclusion visit will include written informed consent, asthma questionnaire, clinical examination, lung function testing, prick tests and assessment of airway remodeling using CT scan and MRI. Bronchial specimens from all subjects will be obtained by fiberoptic bronchoscopy. Airway remodeling will be evaluated by morphological analysis. After BSM cell culture, BSM cells function will be assessed in vitro in the absence or presence of benralizumab using proliferation (BrdU) and chemotactism experiments, ELISA, RT-PCR (polymerase chain reaction ) and electronic microscopy.
- Conditions
- Asthma
- Being tested
- Endobronchial biopsy
- Keywords
- Asthma, remodeling, IL-5 receptor, smooth muscle, biotherapy
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endobronchial biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Endobronchial biopsy | |
| non-severe asthma | • Diagnosis of non-severe asthma according to the Global Initiative for Asthma (GINA). Receives: 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%. Receives: Procedure: Endobronchial biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 12
Secondary outcomes (10)
Number of cultured BSM cell from non-severe asthmatics and healthy volunteers measured using BrdU incorporation.
Determine the proliferation of cultured BSM cell from non-severe asthmatics and healthy volunteers measured using BrdU incorporation.
Measured: Month 12
Number of different genes
Gene expression within BSM cells (RT-PCR, nCCounter Immunology panels)
Measured: Month 12
Measure the inflammatory mediators and extracellular components
Production of inflammatory mediators and extracellular components by cultures BSM cells (ELISA, bio-Plex® Multiples Immunoassays)
Measured: Month 12
Measure the fluorescence intensity of IL-5 receptor subunit alpha on BSM cells
Determine of expression of IL-5 receptor subunit alpha on BSM cells (% of positive cells, mean fluorescence intensity) using flow cytometry
Measured: Month 12
Count the number of mitochondria / BSM area (x107/mm2)
Determine of number of mitochondria / BSM area (x107/mm2) and mitochondrial density using electron microscopy
Measured: Month 12
Count the number of eosinophils/smooth muscle area using optic microscopy
Histological criteria: BSM area (% of tissue area), number of eosinophils/smooth muscle area using optic microscopy
Measured: Month 12
Measure the bronchial dimension by CT-scan
Bronchial dimensions assessed by CT-scan
Measured: Month 12
Measure the bronchial dimension by MRI
Bronchial dimensions assessed by MRI
Measured: Month 12
Measure the lung low single intensity and low attenuation values using MRI
Determine the Lung low single intensity and low attenuation values using MRI
Measured: Month 12
Measure the lung low single intensity and low attenuation values using CT-scan
Determine the Lung low single intensity and low attenuation values using CT-scan
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2020
- Study start23 Sep 2020
- Primary completion5 Oct 2024 (estimated)
- Study completion5 Oct 2024 (estimated)
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 Hospital, BordeauxThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre-Olivier GIRODET, MD, PhD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04365205
- Sponsor's protocol ID
- CHUBX 2019/34
- Acronym
- BENRAMOD
- Status last verified
- Feb 2024
- First submitted
- 23 Apr 2020
- Last updated
- 6 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Benralizumab on Airway Remodeling in Asthma
- ClinicalTrials.gov ID
- NCT04365205
- Acronym / sponsor ID
- BENRAMOD / CHUBX 2019/34
- Conditions
- Asthma
- Keywords
- Asthma, remodeling, IL-5 receptor, smooth muscle, biotherapy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 23 Sep 2020 (actual)
- Primary completion
- 5 Oct 2024 (estimated)
- Study completion
- 5 Oct 2024 (estimated)
- First posted
- 28 Apr 2020 (actual)
- 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 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.
Detailed description
Sixty subjects will be recruited: 20 patients with severe asthma patients, 20 patients with non-severe asthma and 20 non-asthmatic controls. Inclusion visit will include written informed consent, asthma questionnaire, clinical examination, lung function testing, prick tests and assessment of airway remodeling using CT scan and MRI. Bronchial specimens from all subjects will be obtained by fiberoptic bronchoscopy. Airway remodeling will be evaluated by morphological analysis. After BSM cell culture, BSM cells function will be assessed in vitro in the absence or presence of benralizumab using proliferation (BrdU) and chemotactism experiments, ELISA, RT-PCR (polymerase chain reaction ) and electronic microscopy.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| severe asthma | – | Procedure: Endobronchial biopsy* 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. |
| non-severe asthma | – | Procedure: Endobronchial biopsy• Diagnosis of non-severe asthma according to the Global Initiative for Asthma (GINA). |
| non-asthmatic controls | – | Procedure: Endobronchial biopsy* 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%. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (24 listed)
- 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:
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 |
|---|---|---|
| Endobronchial biopsyEndobronchial 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. | Procedure or surgery | non-asthmatic controls, non-severe asthma, severe asthma |
Primary outcome
Number of Bronchial smooth muscle (BSM) cells obtained from severe asthmatics measured in vitro using BrdU incorporation.
Time frame: Month 12
Determine the proliferation of BSM cells obtained from severe asthmatics measured in vitro using BrdU incorporation.
10 secondary outcomes
Number of cultured BSM cell from non-severe asthmatics and healthy volunteers measured using BrdU incorporation.
Time frame: Month 12
Number of different genes
Time frame: Month 12
Measure the inflammatory mediators and extracellular components
Time frame: Month 12
Measure the fluorescence intensity of IL-5 receptor subunit alpha on BSM cells
Time frame: Month 12
Count the number of mitochondria / BSM area (x107/mm2)
Time frame: Month 12
Count the number of eosinophils/smooth muscle area using optic microscopy
Time frame: Month 12
Measure the bronchial dimension by CT-scan
Time frame: Month 12
Measure the bronchial dimension by MRI
Time frame: Month 12
Measure the lung low single intensity and low attenuation values using MRI
Time frame: Month 12
Measure the lung low single intensity and low attenuation values using CT-scan
Time frame: Month 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
- 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.
Pierre-Olivier GIRODET, MD, PhD principal investigator
University Hospital, Bordeaux
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 Hospital, Bordeaux at 1 site in France.
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 19 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 6 Feb 2024. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pierre-Olivier GIRODET, MD, PhD (+33 5 57 62 31 94, pierre-olivier.girodet@u-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Bronchial smooth muscle (BSM) cells obtained from severe asthmatics measured in vitro using BrdU incorporation. (time frame: Month 12). 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 6 Feb 2024.