Severe Asthma Clinical Trial
Official title:
Flow Cytometry Analysis of Eosinophils Activity and Membrane Receptors Expression in Severe Asthma Patients: Basal Characterization and Evaluation of Changes Induces by Biological Drugs.
NCT number | NCT05001529 |
Other study ID # | EoAG |
Secondary ID | |
Status | Recruiting |
Phase | Phase 4 |
First received | |
Last updated | |
Start date | March 18, 2021 |
Est. completion date | March 2023 |
Asthma is a heterogeneous disease, characterized by reversible airflow obstruction, airway hyperresponsiveness, and airway inflammation, in which 40% of patients exhibit eosinophil-driven pathobiology.The main treatment of asthma is the use of corticosteroid, whose use induces a reduction in eosinophils that is considered a strong predictor of response to treatment. Corticosteroids have remained the mainstay treatment of asthma and reduction in eosinophils has remained the unequivocal predictor of steroid response. The prevalence of asthma, which is expected to increase, it is about 300 million people worldwide. About 5-10% of asthma patients have severe disease, which is defined as asthma that requires high-dose inhaled corticosteroids (ICSs) plus a second controller to prevent it from becoming "uncontrolled" or which remains "uncontrolled" despite this therapy. Patients with severe disease have worse quality of life, and disproportionately high morbidity, mortality, and use of health care resources when compared with their peers with well-controlled disease.The pathophysiology of asthma is complex and heterogeneous between patients, as the disease itself; however, on the basis of immune system involvement, it is possible to define 2 subtypes - or endotypes- of asthma. These endotypes are named T2 (for type 2 cells) high or low, and are defined by the levels of expression of the T2 cytokines, IL-4, IL-5, and IL-13 produced by T helper 2 lymphocytes, and innate lymphoid cell-2.T2 high endotype patients display an increase in the number of blood and sputum eosinophils, and have a better response to the current available biological therapies , such as the administration of mepolizumab (anti IL-5 antibody). Eosinophilic asthma is associated to a more severe clinical phenotype,but patients with a T2 endotype respond better to biological therapies. The hypothesis of the present proposal is that the activation status of these cells, analyzed by the expression of activation markers, can be used to define a new, different, endotype, in which eosinophils, although quantitatively low or normal, are qualitatively more active and aggressive, and could therefore act as an indicator of the progression toward a T2 high endotype.Moreover, the investigators will verify whether a different expression of these molecules on eosinophil's surface might be associated with different clinical response to biologic medications.
Status | Recruiting |
Enrollment | 80 |
Est. completion date | March 2023 |
Est. primary completion date | March 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - proved diagnosis of severe, refractory eosinophilic asthma, according to GINA recommendations and International ERS/ATS guidelines; - agreeing to participate this study and signing an informed consent. Exclusion Criteria: - current smoking habit (both tobacco and e-cigarettes), - concomitant diseases requiring chronic administration of immunosuppressors, biologic medications or systemic corticosteroids for any disease other than asthma - History of previous or concomitant acute or chronic disease known to directly or indirectly affect eosinophil count, both in a quantitative and qualitative manner (eosinophilic lung and gastrointestinal diseases, systemic vasculitis, allergic bronchopulmonary aspergillosis, parasitic infections, etc) - COPD/Asthma overlap. - Inability or denial to sign the informed consent. |
Country | Name | City | State |
---|---|---|---|
Italy | Campus Bio Medico University and Teaching Hospital | Roma |
Lead Sponsor | Collaborator |
---|---|
Scarlata, Simone, M.D. | IRCCS San Raffaele |
Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Measurement by flow cytometry of differences in the percentages of eosinophils expressing activation-related molecules | The presence of activated eosinophils will be evaluated by flow cytometry analysis of the expression of CD193, CD63, CD294, CD125, and HLA-DR on eosinophils membrane. Results will be expressed in term of percentage (%) of eosinophils expressing the molecules; |
12 months | |
Primary | Measurement by flow cytometry of the expression levels of activation markers on eosinophils membrane | Activation-associated membrane markers (CD193, CD63, CD294, CD125, and HLA-DR) on eosinophils membrane will be evaluated by flow cytometry and results will be expressed in term of Mean Fluorescence intensity (MFI) of the molecules. MFI is a measure of the amount of the molecule expressed on eosinophils membrane: the higher the MFI, the higher the density of molecules on cellular membrane. The values will be expressed as arbitrary units (AU), defined by the instrument, comparing the samples with a negative (unstained) control. |
12 months | |
Secondary | Correlation between activated eosinophils phenotype and disease progression | Statistical analysis will be used to define the possible correlation between expression of activation markers on eosinophils (as described in primary outcomes 1 and 2) and the clinical status of the patients, evaluated by Flow volume curve, Residual volume, Ig E and eosinophils' count, 6 minutes walking test. | 12 months | |
Secondary | Change in the percentage of activated eosinophils in the group of patients receiving the biological treatment. | Flow cytometry analysis of eosinophils will be performed before and after one year of treatments with antibodies against IL-5 or IL-5R. Percentages of activated eosinophils will be measured as described in Primary outcome | 12 months |
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