AsthmaCaPHeNCT05972213
Phenotypic and Functional Characterization of Neutrophils and Eosinophils in Severe Asthma Treated With Biotherapy
An observational study of Asthma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Neutrophils and eosinophils can have different functions. Depending on their environment, they can be more or less active, with more or less inflammatory activity. Biotherapies can reduce the number of inflammatory cells in the blood and bronchi. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Asthma
- How many people
- 105 participants
- Where
- 1 siteFrance
- Study dates
- 21 Jul 2023to 21 May 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Severe asthmatic patients followed in the Pneumology A department at Bichat Hospital.
Who may be able to join
- 18 years ≤ Age < 85 years
- Severe asthma as defined by ERS/ATS (European Respiratory Society/American Thoracic Society) 2014: asthma requiring high doses of ICS (inhaled corticosteroid) combined with another control therapy (such as long-acting bronchodilators), whether or not patients are controlled
- Longitudinal group:
- Uncontrolled asthma: ACT score < 20 and/or at least one exacerbation in the last 6 months
- Naïve about biotherapy
- Indication for the initiation of biotherapy according to the referring pulmonologist (omalizumab, mepolizumab, benralizumab, dupilumab)
Show all 9Show fewer
- Cross-sectional group:
- Patient on biotherapy (omalizumab, mepolizumab, benralizumab, dupilumab) for at least 6 months.
- Controlled asthma (ACT > 20 and no exacerbation for 6 months) or uncontrolled asthma (ACT < 20 and/or at least 1 exacerbation for 6 months).
Who cannot join
- Refusal to participate or opposition to data processing
- Patient under guardianship or with curators
- Patient on immunosuppressant (other than corticosteroids)
- Treatment with biotherapy for another indication
- Patient not affiliated to a social security scheme or state medical aid
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hôpital Bichat-Claude Bernard
Paris, 75018
Camille Taillé, MD, PhD, 01 40 25 68 63, camille.taille@aphp.fr
About this study
Neutrophils and eosinophils can have different functions. Depending on their environment, they can be more or less active, with more or less inflammatory activity.
Biotherapies can reduce the number of inflammatory cells in the blood and bronchi. However, it is not known whether they have the ability to modify the functions of the remaining cells.
The aim of this study is to better understand the functioning of eosinophilic and neutrophil polynuclear drugs involved in the response to biotherapies in severe asthma. The hypothesis is that biotherapies modify the inflammatory functions of polynuclear cells, which would contribute to the effect of the drug on asthma.
Read the detailed description
Between 3 and 10% of adult asthmatics have a severe form of the disease. The pathophysiology of asthma is dominated by chronic bronchial inflammation of type "T2"" with eosinophil infiltration whose role in bronchial reshuffling, hyperresponsiveness and maintenance of inflammation has been well documented. They are specifically targeted by monoclonal antibodies to IL (inter leukin)-5, IL-5R and IL-4/13.
There is a population of severe asthmatics called "non-T2" characterized by Th17 inflammation, production of IL-6, IL-8, IL-11, GM-CSF (Granulocyte-macrophage colony-stimulating factor) and IL-17 and preponderant bronchial recruitment of neutrophils, resulting in greater clinical severity and decreased sensitivity to corticosteroids. Neutrophils, not specifically targeted by the current therapies used, release reactive forms of oxygen, proteases, neutrophil extracellular traps (NETs) contributing to airway inflammation. The phenotypic heterogeneity, functional heterogeneity and plasticity of neutrophils has been studied in other pathologies but not specifically in asthma.
The response to biotherapies is not always optimal with a significant number of failures or escapes in clinical practice.
There are limited data on these eosinophilic and neutrophil leukocyte subpopulations in asthma, including phenotypic changes under biotherapies. Cellular functions have not been studied under treatment and clinical response is unknown. In addition, neutrophils and eosinophils are most often studied separately, while both cell types contribute to inflammation and can regulate each other.
This study hypothesize an impact of severe asthma biotherapies on the subpopulations and functionality of polynuclear drugs, contributing to the observed therapeutic effect.
This work could lead to a better understanding of the mechanisms of response to biotherapies.
- Conditions
- Asthma
- Keywords
- severe asthma, biotherapies
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Longitudinal group | 25 patients anticipated. Patients with : * Uncontrolled asthma: ACT score < 20 and/or at least one exacerbation in the last 6 months * Naïve biotherapy * Indication for initiation of biotherapy according to the referring pulmonologist (omalizumab, mepolizumab, benralizumab, dupilumab) | |
| Cross-sectional group | 80 patients anticipated. * Patient on biotherapy (omalizumab, mepolizumab, benralizumab, dupilumab) for at least 6 months. * Controlled asthma (ACT > 20 and no exacerbation for 6 months) or uncontrolled asthma (ACT < 20 and/or at least 1 exacerbation for 6 months). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of the difference between the studied parameters of polynuclear cells measured at 6 months compared to those measured at the start of biotherapy.
The main objective will be to characterize the longitudinal evolution of markers measured at 6 months after initiation of biotherapy.
These parameters will be studied on a fresh blood sample collected peripherally on a 7 mL EDTA (Ethylenediaminetetraacetic acid) tube and 5 mL dry tube on the day of inclusion at the time of day hospital or pulmonology consultation, before initiation and during a follow-up pneumology consultation/day hospital at 6 months post-initiation.
Measured: 3 months for the longitudinal group and 9 months for the cross-sectional group
Secondary outcomes (3)
Measure the level of asthma control 6 months after the start of treatment, defined by the ACT score
Secondary objectives will be to measure an association of markers
Measured: 3 months for the longitudinal group and 9 months for the cross-sectional group
Measure the number of exacerbations in the previous 6 months
Secondary objectives will be to measure an association of markers
Measured: 3 months for the longitudinal group and 9 months for the cross-sectional group
Measure the type of biotherapy used
Secondary objectives will be to measure an association of markers
Measured: 3 months for the longitudinal group and 9 months for the cross-sectional group
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start21 Jul 2023
- Primary completion21 Apr 2024 (estimated)
- Study completion21 May 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 Assistance Publique - Hôpitaux de ParisThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Camille Taillé, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05972213
- Sponsor's protocol ID
- APHP230345
- Acronym
- CaPHe
- Status last verified
- Jan 2024
- First submitted
- 4 Jul 2023
- Last updated
- 5 Jan 2024
- 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 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypic and Functional Characterization of Neutrophils and Eosinophils in Severe Asthma Treated With Biotherapy
- ClinicalTrials.gov ID
- NCT05972213
- Acronym / sponsor ID
- CaPHe / APHP230345
- Conditions
- Asthma
- Keywords
- severe asthma, biotherapies
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 21 Jul 2023 (actual)
- Primary completion
- 21 Apr 2024 (estimated)
- Study completion
- 21 May 2024 (estimated)
- First posted
- 2 Aug 2023 (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.
Neutrophils and eosinophils can have different functions. Depending on their environment, they can be more or less active, with more or less inflammatory activity.
Biotherapies can reduce the number of inflammatory cells in the blood and bronchi. However, it is not known whether they have the ability to modify the functions of the remaining cells.
The aim of this study is to better understand the functioning of eosinophilic and neutrophil polynuclear drugs involved in the response to biotherapies in severe asthma. The hypothesis is that biotherapies modify the inflammatory functions of polynuclear cells, which would contribute to the effect of the drug on asthma.
Detailed description
Between 3 and 10% of adult asthmatics have a severe form of the disease. The pathophysiology of asthma is dominated by chronic bronchial inflammation of type "T2"" with eosinophil infiltration whose role in bronchial reshuffling, hyperresponsiveness and maintenance of inflammation has been well documented. They are specifically targeted by monoclonal antibodies to IL (inter leukin)-5, IL-5R and IL-4/13.
There is a population of severe asthmatics called "non-T2" characterized by Th17 inflammation, production of IL-6, IL-8, IL-11, GM-CSF (Granulocyte-macrophage colony-stimulating factor) and IL-17 and preponderant bronchial recruitment of neutrophils, resulting in greater clinical severity and decreased sensitivity to corticosteroids. Neutrophils, not specifically targeted by the current therapies used, release reactive forms of oxygen, proteases, neutrophil extracellular traps (NETs) contributing to airway inflammation. The phenotypic heterogeneity, functional heterogeneity and plasticity of neutrophils has been studied in other pathologies but not specifically in asthma.
The response to biotherapies is not always optimal with a significant number of failures or escapes in clinical practice.
There are limited data on these eosinophilic and neutrophil leukocyte subpopulations in asthma, including phenotypic changes under biotherapies. Cellular functions have not been studied under treatment and clinical response is unknown. In addition, neutrophils and eosinophils are most often studied separately, while both cell types contribute to inflammation and can regulate each other.
This study hypothesize an impact of severe asthma biotherapies on the subpopulations and functionality of polynuclear drugs, contributing to the observed therapeutic effect.
This work could lead to a better understanding of the mechanisms of response to biotherapies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Longitudinal group | – | –25 patients anticipated. Patients with : * Uncontrolled asthma: ACT score < 20 and/or at least one exacerbation in the last 6 months * Naïve biotherapy * Indication for initiation of biotherapy according to the referring pulmonologist (omalizumab, mepolizumab, benralizumab, dupilumab) |
| Cross-sectional group | – | –80 patients anticipated. * Patient on biotherapy (omalizumab, mepolizumab, benralizumab, dupilumab) for at least 6 months. * Controlled asthma (ACT > 20 and no exacerbation for 6 months) or uncontrolled asthma (ACT < 20 and/or at least 1 exacerbation for 6 months). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Severe asthmatic patients followed in the Pneumology A department at Bichat Hospital.
Key inclusion criteria (9 listed)
- 18 years ≤ Age < 85 years
- Severe asthma as defined by ERS/ATS (European Respiratory Society/American Thoracic Society) 2014: asthma requiring high doses of ICS (inhaled corticosteroid) combined with another control therapy (such as long-acting bronchodilators), whether or not patients are controlled
- Uncontrolled asthma: ACT score < 20 and/or at least one exacerbation in the last 6 months
- Naïve about biotherapy
- Indication for the initiation of biotherapy according to the referring pulmonologist (omalizumab, mepolizumab, benralizumab, dupilumab)
Key exclusion criteria (5 listed)
- Refusal to participate or opposition to data processing
- Patient under guardianship or with curators
- Patient on immunosuppressant (other than corticosteroids)
- Treatment with biotherapy for another indication
- Patient not affiliated to a social security scheme or state medical aid
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Measurement of the difference between the studied parameters of polynuclear cells measured at 6 months compared to those measured at the start of biotherapy.
Time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
The main objective will be to characterize the longitudinal evolution of markers measured at 6 months after initiation of biotherapy. These parameters will be studied on a fresh blood sample collected peripherally on a 7 mL EDTA (Ethylenediaminetetraacetic acid) tube and 5 mL dry tube on the day of inclusion at the time of day hospital or pulmonology consultation, before initiation and during a follow-up pneumology consultation/day hospital at 6 months post-initiation.
3 secondary outcomes
Measure the level of asthma control 6 months after the start of treatment, defined by the ACT score
Time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
Measure the number of exacerbations in the previous 6 months
Time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
Measure the type of biotherapy used
Time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 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.
Camille Taillé, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Assistance Publique - Hôpitaux de Paris 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 9 inclusion and 5 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 5 Jan 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 Camille Taillé, MD, PhD (01 40 25 68 63, camille.taille@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of the difference between the studied parameters of polynuclear cells measured at 6 months compared to those measured at the start of biotherapy. (time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group). 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 5 Jan 2024.