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

Status: Not yet recruiting
Location: See location...
Study Type: Observational
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 70
View:

• 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

Locations
Other Locations
United Kingdom
Royal Brompton & Harefield NHS Trust,
London
Contact Information
Primary
Sally Meah, SRN
Sally.Meah@imperial.ac.uk
0207 3518051
Backup
Pankaj K Bhavsar, PhD
p.bhavsar@imperial.ac.uk
02075947961
Time Frame
Start Date: September 1, 2020
Estimated Completion Date: August 31, 2023
Participants
Target number of participants: 66
Related Therapeutic Areas
Sponsors
Leads: Imperial College London

This content was sourced from clinicaltrials.gov

Similar Clinical Trials