Severe Asthma Clinical Trial
— P-CLESAOfficial title:
P-CLESA: Phenotyping Circulating and Lung Resident Eosinophils in Severe Asthma
Title: Phenotyping circulating and lung resident eosinophils in severe asthma (3 years).
Background: Asthma is a long-term condition that affects the airways. When a person with
asthma comes into contact with something that irritates their sensitive airways, the lungs
respond with contracting the muscles around the airway tubes, an inflammation process and
mucus production. The airway will become narrower and inflamed making it hard to breathe and
results in symptoms such as wheezing and coughing. The treatment of asthma consists of using
inhalers that work to widen the airway to relief these symptoms. Often severe asthmatics have
difficulty in controlling their disease, despite good medical care and taking asthma
medicines. At the moment there is no cure for asthma. A new medicine called Mepolizumab
(anti-Interleukin(IL)-5 therapy) has now shown to improve the symptoms of asthma particularly
patients with severe asthma in whom the normal medicines prescribed for asthma are not highly
effective in controlling their disease. You have been chosen receive this new medicine as we
believe it will improve the control of your disease. The aim for this study is to understand
the effect of Mepolizumab on a particular type of cell, called an eosinophil, which in
present lungs and blood of all people but is increased in asthma patients.
Rationale: The relationship between subsets of circulating and lung resident eosinophils in
severe asthma and Mepolizumab (anti-IL-5 therapy) efficacy has not been explored.
Objectives: To determine the gene expression and release of inflammatory proteins (mediator
profiles) of eosinophils from the circulation and the lung, specifically blood and tissue
resident, in patients with severe asthma at baseline and on Mepolizumab therapy.
Study 1: Phenotype subsets of circulating eosinophils in patients with severe asthma at one
time-point Recruit: 15 biologic naïve SA and 15 SA currently on Mepo therapy. Blood
eosinophils will be isolated by negative selection. Single-cell RNA-seq 10xGenomics and
bulk-RNA-seq to be used to simultaneously measure gene and cell surface protein expression in
the same cell to understand cellular heterogeneity in asthmatic eosinophils and identify
novel targets and biomarkers for non-responsiveness Study 2: Phenotype subsets of circulating
and lung eosinophils in patients with severe asthma on Mepolizumab therapy over one year.
Treat 30 appropriately characterised severe asthmatics (Eos>300/ul) with Mepolizumab Blood
eosinophils will be isolated by negative selection. Single-cell RNA-seq 10xGenomics and bulk
-RNA -seq to be used to understand cellular heterogeneity in asthmatic eosinophils post Mepo
Therapy. Sampling at baseline, 3 and 12 months post Mepo Therapy.
Bronchoscopy performed on 30 patients, sampling endobronchial lung biopsy at baseline and 1
yr post Mepo Therapy. Single-cell RNA-seq 10xGenomics on lung resident eosinophils at
baseline and 1yr post Mepolizumab therapy. Immunohistochemistry will also be performed to
characterise cellular content and structure.
Status | Not yet recruiting |
Enrollment | 66 |
Est. completion date | August 31, 2023 |
Est. primary completion date | February 28, 2023 |
Accepts healthy volunteers | |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility |
Inclusion Criteria: - Male or female subject aged between 18 years and 70 years. - Give written informed consent prior to participation in the study including all of its procedures. - Comply with study protocol requirements - Able to read, comprehend, and write at a sufficient level to complete study related materials. - Able to complete the study and all measurements. - All participants have been through a severe asthma protocol that have ascertained the diagnosis of severe asthma, maximised treatments and ensured adherence to therapy. - Stable asthma therapy for at least a month before screening - On <10 mg maintenance OCS therapy Exclusion criteria: Subjects will not be eligible if any of the following apply: - - As a result of medical interview, physical examination or screening investigation the investigators consider the subject unfit either because of risk to the subject due to the study or the influence this may have on the study results. - A history of recreational drug use or allergy which in the opinion of the investigators contra-indicates their participation. - Participation within 3 months in any a trial testing a new molecular entity or drug. - Those, in the opinion of the investigator, who may prove non-compliant with study procedures. - Within 4 weeks of screening visit been hospitalized or required high dose oral corticosteroid (>30 mg prednisolone per day) therapy, asthma not been stable. - Participants who have had prior treatment with bronchial thermoplasty, defined as completion of all thermoplasty treatment sessions within 6 months of screening - History of significant pulmonary disease other than severe asthma. - History of pulmonary eosinophilic syndrome or hyper eosinophilic syndrome. - History of bronchopulmonary aspergillosis Exclusion Criteria: - |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Royal Brompton & Harefield NHS Trust, | London |
Lead Sponsor | Collaborator |
---|---|
Imperial College London |
United Kingdom,
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* Note: There are 24 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phenotype subsets of circulating eosinophils from participants with severe asthma at one time-point | Determine the transcriptomic and mediator profiles of eosinophils from the circulation, specifically blood, in participants with severe asthma on Mepolizumab therapy. | 18 months | |
Primary | Phenotype subsets of circulating and lung eosinophils from participants with severe asthma on Mepolizumab therapy over one year. | Determine the transcriptomic and mediator profiles of eosinophils from the circulation and the airway, specifically blood and tissue resident, in participants with severe asthma at baseline and on Mepolizumab therapy at one year. | 3 years |
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