Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05144087
Other study ID # RHM MED1765
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date December 2021
Est. completion date October 2024

Study information

Verified date November 2021
Source University Hospital Southampton NHS Foundation Trust
Contact Hitasha Rupani, BM PhD
Phone +44 23 8120 4479
Email h.rupani@nhs.net
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The IRIS study aims to investigate the way Mepolizumab affects the structure of the airway cells in patients with Severe Eosinophilic Asthma and how the immune function of these cells changes with treatment. The aim is to take samples of cells from the airways before starting Mepolizumab and after 6 months of treatment. These samples will be taken during a bronchoscopy (a camera test looking into the lungs) and we will analyse these cells in the laboratory. These investigations will allow us to better understand how Mepolizumab affects the cells within the airways.


Description:

IRIS is a prospective observational study investigating Mepolizumab in the treatment of severe eosinophilic asthma. Eosinophilic airway inflammation has been implicated in the pathogenesis of asthma and is particularly relevant in severe eosinophilic asthma (SEA), in which standard asthma therapies fail to adequately control the disease. In severe asthma, there is bronchial epithelial damage and loss of tight junction integrity, goblet cell hyperplasia, enhanced collagen generation within the airway wall and impaired innate immune responses. Mepolizumab has been shown to reduce exacerbations and improve disease control in SEA but there are no studies assessing the impact of Mepolizumab on structural airway cell activity and function and airway remodelling processes. Primary Objective: To investigate changes within bronchial epithelial cells following completion of 6 months (7 doses) of Mepolizumab using single cell RNA sequencing (scRNA-seq) and Frac-seq (subcellular fractionation and RNA-sequencing). Secondary Objectives: To investigate the following after completing treatment with 6 months of Mepolizumab: i) Changes in epithelial barrier integrity using Frac-seq, transepithelial resistance ii) Changes in epithelial antiviral responses fusing Frac-seq in unstimulated and virus-infected cells. iii) Changes in airway remodelling by assessing the profile of fibroblasts isolated from bronchial biopsies employing Frac-seq and immunostaining of bronchial biopsies iv) Evaluate the impact on peripheral airways by obtaining bronchoalveolar lavage (BAL) and peripheral airway brushings for Frac-seq analysis and protein analysis v) Peripheral airway dysfunction using impulse oscillometry Exploratory Objectives i) Evaluation of neural structural changes using biopsies


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 18
Est. completion date October 2024
Est. primary completion date April 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 90 Years
Eligibility Inclusion Criteria: 1. Diagnosis of Severe Eosinophilic Asthma (as per Southampton Severe Asthma MDT and based on ATS/ERS consensus criteria) 2. Approved for treatment with Mepolizumab by Southampton Severe Asthma MDT (in accordance with NICE TA 431) - Blood eosinophil count is =0.3 x109cells/L in preceding 12 months - =4 asthma exacerbations needing systemic steroids in the preceding 12 months 3. Age =18 years 4. Able to provide written informed consent Exclusion Criteria: 1. On maintenance daily oral steroids, asthma immune modulators 2. On long-term systemic antibiotics or antifungal treatment 3. Current smoker or ex-smoker with >10 pack year smoking history 4. Known clinically significant respiratory disorder such as bronchiectasis, interstitial lung disease, allergic bronchopulmonary aspergillosis 5. Currently pregnant or planning pregnancy within the treatment period or breast-feeding 6. History of psychiatric, medical or surgical disorders that in the opinion of the chief investigator may interfere with undergoing a bronchoscopy or may compromise study completion or data collection 7. Current malignancy 8. Alcohol or recreational drug abuse 9. Diagnosis of immunodeficiency requiring treatment 10. Previous bronchial thermoplasty 11. Previous treatment with biological therapy 12. Previously unable to tolerate a bronchoscopy 13. Current or recent (within the last 12 weeks) infection with SARS-CoV-2 14. Unable to provide written informed consent

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
n/a

Sponsors (3)

Lead Sponsor Collaborator
University Hospital Southampton NHS Foundation Trust King's College London, University of Southampton

Outcome

Type Measure Description Time frame Safety issue
Other Evaluation of neural structural changes using immunostaining on biopsy specimens Immunostaining will be reported as mean fluorescence intensity and percentage of cells stained 36 months
Primary To investigate molecular changes in the bronchial epithelium that occurs with mepolizumab treatment using RNA sequencing Changes at the level of single cell RNA sequencing will be reported as:
Changes in the percentage of cell populations present in the airways
Normalised gene counts
36 months
Secondary Changes in epithelial barrier integrity using transepithelial resistance Transepithelial resistance measures changes in voltage across the epithelial cells 36 months
Secondary Changes in epithelial antiviral responses using interferon and other antiviral gene measurements Gene expression will be measured using RNA sequencing and reported as gene counts 36 months
Secondary Changes in airway remodelling by assessing fibroblasts isolated from bronchial biopsies using RNA sequencing RNA sequencing will be reported as gene counts 36 months
Secondary Changes in airway remodelling by assessing fibroblasts isolated from bronchial biopsies using immunostaining Immunostaining will be reported as mean fluorescence intensity and percentage of cells stained 36 months
Secondary Evaluate the impact of Mepolizumab on peripheral airways by obtaining bronchoalveolar lavage for RNA sequencing RNA sequencing will be reported as gene counts 36 months
Secondary Evaluate the impact on peripheral airways by obtaining peripheral airway brushings for RNA sequencing RNA sequencing will be reported as gene counts 36 months
Secondary Peripheral airway dysfunction using impulse oscillometry Impulse oscillometry will be measured as resistance and impedance 36 months
See also
  Status Clinical Trial Phase
Completed NCT04742504 - Interaction Between Benralizumab and Basophils in Eosinophilic Asthma
Recruiting NCT04565483 - Predictive Signature of Benralizumab Response Phase 4
Completed NCT04181190 - Effects of Anti-IL5 Biological Treatments on Blood IgE Levels in Severe Asthmatic Patients
Recruiting NCT05787678 - Dupilumab Efficacy on Bronchial Inflammation, Small Airways Disfunction and Mucous Secretion
Completed NCT04456270 - Asthma Control in a Dutch Primary Care Population
Not yet recruiting NCT05091385 - Efficacy of Mepolizumab in Polish Patients With Severe Eosinophilic Asthma
Recruiting NCT05078281 - Patients With Severe Eosinophilic Asthma Treated With Benralizumab
Recruiting NCT04512521 - Functional Lung MRI for Early Treatment Response Assessment for Patients With Eosinophilic Asthma
Recruiting NCT05813288 - A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3) Phase 3
Recruiting NCT04319705 - Anti-viral Effects of Azithromycin in Patients With Asthma and COPD Phase 4
Recruiting NCT06288516 - BenRalizumab Effect on Airway Remodeling in Severe asTHma Phase 4
Active, not recruiting NCT03733535 - Evaluating the Effect of Benralizumab in Severe, Poorly-controlled Eosinophilic Asthma Using Inhaled Hyperpolarized 129-Xenon MRI N/A
Not yet recruiting NCT05241769 - The Influence of Inhaled CorticoSteroids Adherence on Treatment Response to Mepolizumab in Severe Eosinophilic Asthma
Not yet recruiting NCT04924478 - Evaluation of Volatile Organic Compounds in Mepolizumab Therapy
Recruiting NCT05763121 - A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma. Phase 3
Recruiting NCT05748600 - A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Eosinophilic Asthma Phase 3
Completed NCT03453021 - Effect of Mepolizumab on Decrease of Systemic Corticosteroids in Patients With Severe Eosinophilic Asthma
Active, not recruiting NCT04612556 - Efficacy of Mepolizumab in Severe Asthmatics on a Long Term (MESILICO)
Recruiting NCT05404763 - Mepolizumab and Physical Activity in Severe Asthma
Completed NCT04710134 - Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma Phase 4