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

NCT04463836 | Unknown

• 1 other identifier: P82746
• Study Type: observational
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Severe Asthma

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All the participants identified as being eligible with severe asthma confirmed by a multidisciplinary team in the Royal Brompton Hospital will be invited to take part in the study. Participants referred to the severe asthma clinic will undergo a specific protocol that leads to the ultimate diagnosis of severe asthma as defined by the ERS/ATS guidelines for severe asthma (1). Participants with severe asthma will be diagnosed as persistently poor control and/or exacerbations of asthma despite high dose therapy defined as at least 1000 μg fluticasone propionate equivalent per day and a second controller. The evaluation will include an assessment of adherence to therapies.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Royal Brompton & Harefield NHS Trust,

London, SW3 6HP, United Kingdom

Location

Related Publications (24)

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MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Pankaj K Bhavsar, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sally Meah, SRN

CONTACT

0207 3518051; Sally.Meah@imperial.ac.uk

Pankaj K Bhavsar, PhD

CONTACT

02075947961; p.bhavsar@imperial.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 9, 2020
• Study Start: September 1, 2020
• Primary Completion: February 28, 2023
• Study Completion: August 31, 2023
• Last Updated: July 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 18 months - 4 years from start of study

Locations

GB (1)