NCT04463836: P-CLESA

Phenotyping Circulating and Lung Resident Eosinophils in Severe Asthma (P-CLESA)

Status unknown Last updated 9 July 2020

What this trial tests

trial in Severe Asthma in 66 participants. Status unknown.

Timeline

1 September 2020

Primary endpoint
28 February 2023

31 August 2023

Quick facts

Lead sponsor	Imperial College London
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	66
Start date	1 September 2020
Primary completion	28 February 2023
Estimated completion	31 August 2023
Sites	1 location across United Kingdom

Conditions studied

• Severe Asthma — all drugs for Severe Asthma →

Sponsor

Imperial College London

Who can join

Adults 18 to 70, any sex, with Severe Asthma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.