Asthma
Conditions
Brief summary
The objective of this study is to investigate the effect of dupilumab treatment on mucus plugging in severe asthma patients with severe eosinophilic asthma. Therefore, the investigators plan to apply computer tomography to investigate mucus plugging and thoroughly examine different airway samples from Type 2-high severe asthmatic patients at a cellular, molecular, microbiological and metabolomic level. This study will help to unravel underlying treatment mechanisms of dupilumab therapy in severe asthmatics.
Detailed description
In this prospective exploratory pilot study, the objective is to enroll 10 participants with severe asthma who are candidates for Dupilumab treatment. The study's individual duration will not exceed 26 weeks. Before enrollment, informed consent will be obtained from all subjects. All patients with severe Type 2 Asthma can be included according to inclusion- and exclusion criteria. Those with a history of monoclonal antibody treatment for asthma may be included after a washout period of 2 half-lives or 1 month (whichever is longer). Prior to commencing Dupilumab, the investigators will assess patient-reported outcomes using the Asthma Control Questionnaire (ACQ-6), Asthma Control Test (ACT), and mini Asthma Quality of Life Questionnaire (miniAQLQ). Additionally, the investigators will review concomitant medication, conduct Spirometry, measure fraction of exhaled nitric oxide (FeNO), perform ultra high-resolution computer tomography of the lungs, draw blood for laboratory samples, and carry out bronchoscopy with bronchoalveolar lavage and biopsies. Subsequently, Dupilumab treatment will be initiated, and patients will visit our center every 2 weeks for clinical assessments, including monitoring adverse events, lung function, laboratory samples, and Dupilumab administration. After 22 weeks, the investigators will repeat computer tomography of the lungs and bronchoscopy. For patients who do not experience clinical improvement, Dupilumab treatment will be discontinued after 6 months.
Interventions
DRUGDupilumab
Clinical assessment, lung function, CT-scans and Bronchoscopy prior to and 22 weeks after initiation of Dupilumab.
Sponsors
Medical University of Vienna
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All patients who: * are ≥18 years of age * have a recorded clinical diagnosis of asthma (ICD-10 Code: J45) * meet the requirements for treatment of severe T2-high asthma for Dupilumab defined as: * FeNO \> 25 ppB * two measurements of at least 250 eosinophils /µl in the blood OR one measurement of blood eosinophils at least 250 cells/µl during reduction of OCS dosing if treated with oral corticosteroids and/or one measurement of sputum ≥ 2% or BAL eosinophils ≥ 1% * have a history of treatment with monoclonal antibodies for asthma if a wash out period of 2 half-lives or 1 month (whatever is longer) has passed
Exclusion criteria
Patients who: * are pregnant as determined by a ß-HCG test * have severe anatomic variations or deviations that do not allow bronchoscopy * suffer from additional others confounding underlying lung disorder including but not limited to: Bronchiectasis, chronic obstructive pulmonary disorder (COPD), pulmonary fibrosis, emphysema, Cystic fibrosis, any known parasitic infections and lung cancer. * show pulmonary conditions with symptoms of asthma and blood eosinophilia, including but not limited to: Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, hypereosinophilic syndrome * suffer from a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, * have clinically meaningful comorbidity as determined by the evaluating committee, * experience of an asthma exacerbation within 4 weeks prior to the first main visit * immune disorder and/or immunosuppressive treatment (e.g. cyclosporine), ongoing biological treatment of asthma (e.g., mepolizumab, omalizumab, benralizumab) or last biological treatment 2 half-lives or 1 month before the first main visit * have a history of drug and alcohol abuses * are currently smoking or are former smokers for less than 6 months with \>10 pack years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Dupilumab treatment on mucus plugging in patients with severe eosinophilic asthma | 26 weeks | CT scans of the lungs will be done on baseline and 22 weeks after begin applying ultra-high resolution CT technique (special resolution 0.2 mm). The examinations will be performed as no-contrast CTs in sustained deep inspiration and expiration. The images will be investigated and scored independently by two thoracic radiologists. Both radiologists will score the extent of air-trapping, bronchial wall thickening and mucus plugging per pulmonary segment based on the following scale: * absent (0) * minimal (1) * moderate (2) * extensive (3) Prior to the evaluation of study scans, both radiologists will undergo a consensus reading on CT scans not included in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in asthma control | 26 weeks | We will assess change in asthma control under Dupilumab treatment using the Asthma Control Test (ACT), Asthma Control Questionnaire-6 (ACQ-6) and mini Asthma Quality of Life Questionnaire (mAQLQ). |
| Change in number of asthma exacerbations | 26 weeks | Asthma exacerbations will be defined as events requiring the use of systemic corticosteroids for at least three consecutive days. |
| Change in peripheral blood eosinophil count (PBEC) | 26 weeks | PBEC, measured in cells per microliter (cells/µL), will be assessed every two weeks at the clinic. |
| Change in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) | 26 weeks | FEV₁ and FVC, expressed in milliliters (mL) and as percentages of the predicted values, will be assessed during clinic visits. Additionally, patients will receive home spirometry devices to enable more frequent lung function monitoring between appointments |
| Change in fractional exhaled nitric oxide (FeNO) | 26 weeks | FeNO will be measured daily at home using portable devices, as well as every two weeks at the clinic. Measurements will be expressed in parts per billion (ppb). |
| Change in Inflammatory Mediators | 26 weeks | Quantification of inflammatory mediator concentrations in BAL supernata |
| Change in Transcriptional Profiling | 26 weeks | Analysis of gene expression profiles in BAL cells and lung tissue using transcriptional sequencing techniques. |
| Lung Microbiome | 26 weeks | Assessment of microbial community composition in BAL samples. |
| Metabolomic Profile | 26 weeks | Characterization of metabolite composition in BAL fluid. |
| Change in Cellular Composition and Activation | 26 weeks | Characterization of immune cell populations and their activation states isolated from bronchoalveolar lavage (BAL) cells. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 26 weeks | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
Countries
Austria
Contacts
Primary ContactMarco Idzko, M.D.
Backup ContactSlagjana Stoshikj, M.D.
Outcome results
None listed