DETACT sEvere asThmAtiC paTients - a Pilot Study

Medical University of Vienna10 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Asthma

Interventions

DupilumabDRUG

Clinical assessment, lung function, CT-scans and Bronchoscopy prior to and 22 weeks after initiation of Dupilumab.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Medical University of Vienna, Clinic of Internal Medicine II, Department of Pulmonology

Vienna, Vienna, Austria

RECRUITING

Outcomes

Primary Outcomes

Effect of Dupilumab treatment on mucus plugging in patients with severe eosinophilic asthma

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.

Time frame: 26 weeks

Secondary Outcomes

Change in asthma control

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).

Time frame: 26 weeks

Change in number of asthma exacerbations

Asthma exacerbations will be defined as events requiring the use of systemic corticosteroids for at least three consecutive days.

Time frame: 26 weeks

Change in peripheral blood eosinophil count (PBEC)

PBEC, measured in cells per microliter (cells/µL), will be assessed every two weeks at the clinic.

Time frame: 26 weeks

Change in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)

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

Central Contacts

Marco Idzko, M.D.

CONTACT

+43140400 marco.idzko@meduniwien.ac.at

Slagjana Stoshikj, M.D.

CONTACT

+43140400 slagjana.stoshikj@meduniwien.ac.at

Data from ClinicalTrials.gov

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