nderstanding the effect of mepolizumab treatment on brain imaging and wellbeing in patients with severe asthma

Not Applicable

• Conditions: Asthma; Respiratory

• Registration Number: ISRCTN74240789
• Lead Sponsor: orth Bristol NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-12-04
• Last Update Posted: 19 December 2023
• Study Completion: 2025-05-05

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Cases:
1. Aged 18+ years
2. Physician-diagnosed severe eosinophilic asthma eligible for mepolizumab therapy as per National Institute for Health and Care Excellence guidance 2017, satisfying one of the following criteria:
2.1. Peripheral blood eosinophils =300 cells per microlitre, with =4 exacerbations requiring oral corticosteroids in the previous 12 months or continuous oral corticosteroids of at least the equivalent of prednisolone 5 milligrams per day over the previous 6 months
2.2. Peripheral blood eosinophils =400 cells per microlitre, with =3 exacerbations requiring oral corticosteroids in the previous 12 months or continuous oral corticosteroids of at least the equivalent of prednisolone 5 milligrams per day over the previous 6 months
3. A regional asthma MDT decision was made to start mepolizumab
4. The patient agrees to start mepolizumab and is able to provide written informed consent and participate in the study

Controls:
1. Aged 18+
2. Physician-diagnosed mild or moderate asthma for >3 months, GINA step 2-4
3. Well-controlled asthma defined by an Asthma Control Questionnaire–5 (ACQ-5) =/< 1.5
4. Participant is willing and able to give informed consent to take part in the study

Exclusion Criteria

Cases
1. Current smoking, or a greater than 10 pack-year history of smoking in ex-smokers.
2. A diagnosis of an alternative lung disease, including, but not limited to, allergic bronchopulmonary aspergillosis, eosinophilic granulomatous polyangiitis, bronchiectasis or chronic obstructive pulmonary disease.
3. Previous anti-asthma biological therapies including mepolizumab, benralizumab, omalizumab, reslizumab and dupilimab.
4. Pregnancy/childbearing age not using contraception.
5. Alcohol and drug addiction.
6. CNS diseases the investigators consider would have a significant effect on outcomes – including stroke, MS, epilepsy, tumour or significant cognitive impairment (including dementia, or severe learning disabilities).
7. Participants with contraindications to MRI will not be able to take part in the MRI study, but can be recruited to complete the questionnaires.
8. Contraindications to completing pulmonary function tests.

Controls
1. Oral corticosteroid use in the last 3 months, or =3 oral corticosteroid courses in the last 12 months.
2. Current smoking, or a greater than 10 pack-year history of smoking in ex-smokers.
3. A diagnosis of an alternative lung disease, including, but not limited to, allergic bronchopulmonary aspergillosis, eosinophilic granulomatous polyangiitis, bronchiectasis, chronic obstructive pulmonary disease or interstitial lung disease.
4. Previous anti-asthma biological therapies including mepolizumab, benralizumab, omalizumab, reslizumab, dupilumab or tezepelumab.
5. Pregnancy/childbearing age not using contraception.
6. Alcohol and drug addiction.
7. CNS diseases the investigators consider would have a significant effect on outcomes – including stroke, MS, epilepsy, tumour or significant cognitive impairment (including dementia, or severe learning disabilities).
8. Participants with contraindications to MRI will not be able to take part in the MRI study, but can be recruited to complete the questionnaires.
9. Contraindications to completing pulmonary function tests.

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Brain microstructural imaging (quasi-diffusion) measured with a magnetic resonance imaging brain scan at baseline (case and control) and after 6 months of mepolizumab treatment (case only)