Severe AsthmaMOSAICNCT05616338
Modeling Bronchial Epithelium in Severe Asthma With Human Induced Pluripotent Stem Cells (iPSC)
A study testing Blood sample in people with Severe Asthma and Allergic Bronchopulmonary Aspergillosis (ABPA), run by University Hospital, Montpellier at 1 site in France.
Trial summary
Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Severe Asthma, Allergic Bronchopulmonary Aspergillosis (ABPA)
- What is being tested?
- Blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteFrance
- Study dates
- 29 Nov 2022to 16 Mar 2023
- Phase
- Interventional
- 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
Who may be able to join
- Smoking < 10 BP and weaned > 1 year.
- Diagnostic criteria for Severe asthma group T2 :
- History of severe asthma diagnosed by a physician (according to GINA criteria)
- Subject on high dose inhaled corticosteroid (ICS 1000 µg beclometasone equivalent) and beta-agonists for at least 6 months prior to inclusion
- Blood eosinophilia in history (previous years) > 300/mm3
- Diagnostic criteria for Allergic bronchopulmonary aspergillosis (ABPA) group
Show all 14Show fewer
- Diagnosis of ABPA defined by the following 3 mandatory criteria:
- Diagnosis of asthma by the physician for at least 12 months based on the 2019 recommendations of the Global Initiative for Asthma (GINA) group
- Evidence of hypersensitivity to Aspergillus Fumigatus by skin test (on screening or previous documented positive skin test within the last 12 months), or serum Immunoglobulin E (IgE) specific antibodies to A. Fumigatus (≥ 0.35 kUnit/l) at screening.
- Elevated total serum IgE (> 1000 IU/ml). If the 3 ancillary criteria for the diagnosis of of ABPA (below) are met, an IgE level ≤ 1,000 IU/ml is acceptable. If the patient is receiving oral corticosteroids (OCs) at screening, a previous documented IgE level >1000 IU/ml within the last 12 months is acceptable.
- And at least 2 of the following ancillary criteria:
- Blood eosinophil count >500 cells/μl at screening for patients not receiving OCs at screening. For patients receiving OCs at screening, blood eosinophil count > 500 cells/μl at screening or documented previous eosinophil count > 500 cells/μl in the last 12 months.
- Presence of precipitating antibodies or serum immunoglobulin G (IgG) to A. Fumigatus at screening.
- Documented radiological abnormalities consistent with ABPA (such as transient mucoid impaction, hyperdense mucus [high attenuation of mucous plugs], opacities of centro-lobular nodules attenuation of mucous plugs], opacities of centro-lobular nodules, telectasis, bronchiectasis, etc.) by chest X-ray or high-resolution computed tomography (HR-CT) within the last 18 months or at screening.
Who cannot join
- Other associated respiratory diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis)
- Patient in an exclusion period determined by another protocol
- Protected populations according to the French public health code: Parturient, nursing or pregnant women; subjects deprived of liberty by judicial or administrative decision; Major protected by law (under any form of guardianship).
- Lack of informed consent
- Non-beneficiary of the national health insurance system
Trial locations and contacts
1 site in 1 country.
About this study
Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus.
The development of a model of bronchial epithelium generated from patients with chronic lung disease will allow the modeling of bronchial tissue to understand the formation of these mucus plugs. This study aims to validate this model
Read more
The investigators propose to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments:
Differentiation of an Induced Pluripotent Stem cell (iPSC) clone derived from blood sample (Peripheral Blood Mononuclear Cells) of Type 2 inflammation (T2) severe asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in order to obtain differentiated bronchial epithelia in vitro.
Read the detailed description
Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus.
At the cellular and molecular level, severe asthma and ABPA are chronic bronchial diseases characterized by type 2 (T2) airway inflammation, bronchial smooth muscle hyperplasia, excessive mucus production by mucus cell metaplasia and epithelial remodeling. Type 2 inflammation in asthma is predominant and is characterized by the accumulation of immune cells, such as eosinophils, mast cells, T-helper 2 (Th2) cells, innate lymphoid cells type 2 (ILC2s) and dendritic cells.
Persistent airway obstruction despite maximal therapy is currently considered the greatest unmet medical need in asthma treatment. Fahy and colleagues published a key paper in 2018 that may explain airway obstruction. Using chest CT scans, they demonstrated the presence of mucus plugs that completely occlude segments of the airways of severe asthmatics. These mucus plugs are associated with a high number of circulating eosinophils in the blood.
There is no large-scale model to model severe asthma and ABPA. The investigators propose to develop a bronchial epithelium with pluripotent stem cells (iPSC) in air-liquid interface called iALI generated from these patients in aim to model severe asthma and ABPA and in particular the epithelium.
The secondary objectives aims to answer are:
- Comparison of the iPSC derived airway epithelium with nasal epithelial cells isolated from the same patient (nasal brush).
- To characterize the phenotype of the iPSC derived airway epithelium from ABPA and T2 severe asthma patient, in comparison to a healthy control.
- Differentiation of iPSC into mature eosinophils
- Co culture of the epithelia with iPSC derived eosinophils
- Culture of iPSC derived airway epithelium with Charcot-Leyden crystal
- Demonstrate the feasibility of obtaining iPSC from peripheral blood sampling.
- Being tested
- Blood sample
- Keywords
- Severe asthma, ABPA, Pluripotent stem cells, Airway epithelium, Eosinophils, Crystal
- Medical subject headings
- Asthma, Aspergillosis, Allergic Bronchopulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleOther
Also called nasal brush
A blood sample and a nasal brush for each participant. The nasal brushing will allow the isolation of epithelial cells that will serve as a comparison for the bronchial tissue produced from blood-derived iPS.
A blood sample of approximately 14 ml will be taken for isolation and freezing of the blood mononuclear cells allowing the generation of iPS.
| Study group | Role | What they receive |
|---|---|---|
| Eligible patients | Experimental | Not described Receives: Other: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Obtention of functional bronchial epithelium from iPSC: yes/no
Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood? (yes/no) The achievement of functional bronchial epithelium (iALI) from iPSCs of a T2 severe asthma patient and an ABPA patient will be assessed by quantification of differentiation markers by immunofluorescence, integrity of the bronchial epithelium by measurement of trans-epithelial resistance (TEER), secretory function by measurement of mucin concentrations (CCSP, MUC5AC and MUC5B) and analysis of ciliary beat
Measured: Day 0 + culture (cross-sectional study)
Secondary outcomes (5)
Comparison of the transcriptomic profile between iALI and airway epithelial cells
the transcriptomic profile of iALI from iPSCs of a T2 severe asthma patient and an ABPA patient will be compare to the one of airway epithelial cells from nasal brushing from the same patients
Measured: Day 0 + culture (cross-sectional study)
Comparison of the transcriptomic profile between bronchial epithelia generated from severe asthma patients and from healthy subjects
The transcriptomic profile of iALI from iPSCs of a T2 severe asthma patient and an ABPA patient will be compare to those from healthy subjects
Measured: Day 0 + culture (cross-sectional study)
Differentiation of iPSC into mature eosinophils : yes/no
Characterization of eosinophils obtained from iPSCs of a T2 severe asthma patient and an ABPA patient by the presence of specific markers by flow cytometry, immunohistochemistry and immunofluorescence
Measured: Day 0 + culture (cross-sectional study)
Evaluation of immune cell/bronchial epithelium dialogue
Co culture of the epithelia with iPSC derived eosinophils and the immune cell/bronchial epithelium dialogue in the co-culture of eosinophils with iALI will be evaluated by the activation of eosinophils in contact with the epithelium and by the characterization and study of the phenotype of the exposed epithelium
Measured: Day 0 + culture (cross-sectional study)
Obtention of iPSC from peripheral blood sampling : yes/no
Qualification of blood-derived iPSC lines by morphology, culture behavior, karyotype and expression of specific markers
Measured: Day 0 + culture (cross-sectional study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2022
- Study start29 Nov 2022
- Primary completion16 Mar 2023
- Study completion16 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe AsthmaStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne Sophie GAMEZ, MD, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05616338
- Sponsor's protocol ID
- RECHMPL22_0384
- Other IDs
- 2022-A02059-34
- Acronym
- MOSAIC
- Status last verified
- Aug 2023
- First submitted
- 7 Nov 2022
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study. Data will be made available to persons who address a reasonable request to the study director. Individual participant data (and an accompanying data dictionary) will be deidentified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity.
Publications
Ahmed E, Assou S, Foisset F, Bourdais C, Vanheerswynghels M, Petit A, Gamez AS, Gras D, Chanez P, de Vos J, Hammad H, Bourdin A, Lambrecht B. [Modeling T2 high severe asthma using human induced pluripotent stem cells (hiPSC)]. Rev Mal Respir. 2024 Apr;41(4):289-293. doi: 10.1016/j.rmr.2024.02.012. Epub 2024 Mar 8. French.
PubMed 38461089
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modeling Bronchial Epithelium in Severe Asthma With Human Induced Pluripotent Stem Cells (iPSC)
- ClinicalTrials.gov ID
- NCT05616338
- Acronym / sponsor ID
- MOSAIC / RECHMPL22_0384
- Keywords
- Severe asthma, ABPA, Pluripotent stem cells, Airway epithelium, Eosinophils, Crystal
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 29 Nov 2022 (actual)
- Primary completion
- 16 Mar 2023 (actual)
- Study completion
- 16 Mar 2023 (actual)
- First posted
- 15 Nov 2022 (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.
Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus.
The development of a model of bronchial epithelium generated from patients with chronic lung disease will allow the modeling of bronchial tissue to understand the formation of these mucus plugs. This study aims to validate this model
The investigators propose to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments:
Differentiation of an Induced Pluripotent Stem cell (iPSC) clone derived from blood sample (Peripheral Blood Mononuclear Cells) of Type 2 inflammation (T2) severe asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in order to obtain differentiated bronchial epithelia in vitro.
Detailed description
Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus.
At the cellular and molecular level, severe asthma and ABPA are chronic bronchial diseases characterized by type 2 (T2) airway inflammation, bronchial smooth muscle hyperplasia, excessive mucus production by mucus cell metaplasia and epithelial remodeling. Type 2 inflammation in asthma is predominant and is characterized by the accumulation of immune cells, such as eosinophils, mast cells, T-helper 2 (Th2) cells, innate lymphoid cells type 2 (ILC2s) and dendritic cells.
Persistent airway obstruction despite maximal therapy is currently considered the greatest unmet medical need in asthma treatment. Fahy and colleagues published a key paper in 2018 that may explain airway obstruction. Using chest CT scans, they demonstrated the presence of mucus plugs that completely occlude segments of the airways of severe asthmatics. These mucus plugs are associated with a high number of circulating eosinophils in the blood.
There is no large-scale model to model severe asthma and ABPA. The investigators propose to develop a bronchial epithelium with pluripotent stem cells (iPSC) in air-liquid interface called iALI generated from these patients in aim to model severe asthma and ABPA and in particular the epithelium.
The secondary objectives aims to answer are:
- Comparison of the iPSC derived airway epithelium with nasal epithelial cells isolated from the same patient (nasal brush).
- To characterize the phenotype of the iPSC derived airway epithelium from ABPA and T2 severe asthma patient, in comparison to a healthy control.
- Differentiation of iPSC into mature eosinophils
- Co culture of the epithelia with iPSC derived eosinophils
- Culture of iPSC derived airway epithelium with Charcot-Leyden crystal
- Demonstrate the feasibility of obtaining iPSC from peripheral blood sampling.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eligible patients | Experimental | Other: Blood sample |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Smoking < 10 BP and weaned > 1 year.
- History of severe asthma diagnosed by a physician (according to GINA criteria)
- Subject on high dose inhaled corticosteroid (ICS 1000 µg beclometasone equivalent) and beta-agonists for at least 6 months prior to inclusion
- Blood eosinophilia in history (previous years) > 300/mm3
- Diagnostic criteria for Allergic bronchopulmonary aspergillosis (ABPA) group
Key exclusion criteria (5 listed)
- Other associated respiratory diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis)
- Patient in an exclusion period determined by another protocol
- Protected populations according to the French public health code: Parturient, nursing or pregnant women; subjects deprived of liberty by judicial or administrative decision; Major protected by law (under any form of guardianship).
- Lack of informed consent
- Non-beneficiary of the national health insurance system
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 |
|---|---|---|
| Blood sampleAlso: nasal brushA blood sample and a nasal brush for each participant. The nasal brushing will allow the isolation of epithelial cells that will serve as a comparison for the bronchial tissue produced from blood-derived iPS. A blood sample of approximately 14 ml will be taken for isolation and freezing of the blood mononuclear cells allowing the generation of iPS. | Other | Eligible patients |
Primary outcome
Obtention of functional bronchial epithelium from iPSC: yes/no
Time frame: Day 0 + culture (cross-sectional study)
Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood? (yes/no) The achievement of functional bronchial epithelium (iALI) from iPSCs of a T2 severe asthma patient and an ABPA patient will be assessed by quantification of differentiation markers by immunofluorescence, integrity of the bronchial epithelium by measurement of trans-epithelial resistance (TEER), secretory function by measurement of mucin concentrations (CCSP, MUC5AC and MUC5B) and analysis of ciliary beat
5 secondary outcomes
Comparison of the transcriptomic profile between iALI and airway epithelial cells
Time frame: Day 0 + culture (cross-sectional study)
Comparison of the transcriptomic profile between bronchial epithelia generated from severe asthma patients and from healthy subjects
Time frame: Day 0 + culture (cross-sectional study)
Differentiation of iPSC into mature eosinophils : yes/no
Time frame: Day 0 + culture (cross-sectional study)
Evaluation of immune cell/bronchial epithelium dialogue
Time frame: Day 0 + culture (cross-sectional study)
Obtention of iPSC from peripheral blood sampling : yes/no
Time frame: Day 0 + culture (cross-sectional study)
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 1 Oct 2026.
- Results publication: PubMed 38461089Ahmed E, Assou S, Foisset F, Bourdais C, Vanheerswynghels M, Petit A, Gamez AS, Gras D, Chanez P, de Vos J, Hammad H, Bourdin A, Lambrecht B. [Modeling T2 high severe asthma using human induced pluripotent stem cells (hiPSC)]. Rev Mal Respir. 2024 Apr;41(4):289-293. doi: 10.1016/j.rmr.2024.02.012. Epub 2024 Mar 8. French.
- Individual participant dataSharing planned: Yes. The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study. Data will be made available to persons who address a reasonable request to the study director. Individual participant data (and an accompanying data dictionary) will be deidentified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity.
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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.
Anne Sophie GAMEZ, MD principal investigator
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sample in people with Severe Asthma and Allergic Bronchopulmonary Aspergillosis (ABPA), run by University Hospital, Montpellier 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 14 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: finished, as of the sponsor's last update on 1 Oct 2026. 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?
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?
Obtention of functional bronchial epithelium from iPSC: yes/no (time frame: Day 0 + culture (cross-sectional study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05616338, which also lists 1 linked publication.
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 1 Oct 2026.