Poor Response to Monoclonal Therapy in Asthma

NCT04114396 | Unknown

• 1 other identifier: 18048
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma affects 8% of the entire population. 4-5% of asthma sufferers have severe asthma, characterised by recurrent exacerbations (worsening of symptoms leading to the person having a bout of corticosteroids and/or antibiotics), significant symptoms and lack of response to the most widely used therapy, corticosteroids. There is now new types of treatments (antibody drugs) which are licensed to manage severe asthma such as Anti-IL5. There is evidence Anti-IL5 and other similar antibody drugs are effective at reducing asthma exacerbations and reduce the need for oral corticosteroids for those that have severe asthma. However, some patients respond poorly to Anti-IL5 and the investigators would like to find out why this happens. It is hoped that the investigators can identify the mechanism of poor treatment response to Anti-IL5. It is also hoped that the investigators can understand why symptoms worsen to the point of requiring antibiotics and/or steroids (also known as an exacerbation) for those prescribed Anti-IL5.

Conditions

Asthma

Keywords

Severe Asthma; Anti-IL5; Asthma

Outcome Measures

Primary Outcomes (3)

• Identification of mechanisms associated with poor response to anti-IL5 therapy

  Identification of mechanisms associated with poor response to anti-IL5 therapy. A poor response is defined as an inability to halve the pre-treatment annualised exacerbation rate; an asthma exacerbation is defined as a worsening of asthma symptoms necessitating a short burst of oral corticosteroids, or a doubling of maintenance oral corticosteroid treatment dose.

  12 months

• An improvement in FEV1 as assessed by spirometry

  Treatment response as assessed as a clinically meaningful improvement in asthma control (ACQ change of \>0.5).

  12 months

• A clinically meaningful improvement in asthma control as assessed by ACQ

  An improvement in FEV1 of \>100ml using spirometry.

  12 months

Secondary Outcomes (2)

• The identification of exacerbation pathogenesis in patients receiving anti-IL5 therapy via cytokine analysis

  12 months

• The identification of exacerbation pathogenesis in patients receiving anti-IL5 therapy via viral throat swab analysis

  12 months

Study Arms (2)

Severe asthma

Untreated by anti-IL5 treatment for severe asthma at point of recruitment. To be prescribed anti-IL5 as part of their treatment following consent. Note: Anti-IL5 treatment is prescribed as per agreed multidisciplinary team meeting, outside of the decision to enrol the patient on the study, and is administered by the clinical team as part of the patient's clinical care outside of the research study.

Drug: Anti-IL5 Antibody; Procedure: Bronchoscopy

Healthy control

Control group without respiratory condition

Procedure: Bronchoscopy

Interventions

Anti-IL5 Antibody DRUG

Asthma group: Anti-IL5 treatment Control group: No biologic.

Severe asthma

Bronchoscopy PROCEDURE

Optional for both arms

Healthy control; Severe asthma

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the severe asthma clinic. Once the multidisciplinary team (MDT) have decided that the patient will be prescribed anti-IL5 therapy a patient information sheet (PIS) will be posted out by the clinical team. If the appointment with the clinical team is within days of the MDT, potential participant will be approached by a member of the research team and the study will be discussed and a patient information sheet will be given to the patient. Control participants will be recruited from our Respiratory Research Database and have agreed to be contacted for research. A poster will be created to be put up in Nottingham City Hospital, Queen's Medical Centre and at the University of Nottingham, UK.

You may qualify if:

• Aged 18 - 80 years old
• Able to give informed consent
• All patients identified as being suitable for anti-IL5 therapy by the asthma MDT will be considered for study enrolment.
• This assessment by the MDT for participants to be eligible includes:
• A measure of compliance with current asthma medication,
• Confirmation of asthma diagnosis
• Suitability for anti-IL5 therapy based on blood eosinophil counts,
• Asthma exacerbation rates
• Prednisolone dose.
• Confirmation of treatment requires at least two asthma specialists to agree that this is the correct course of action
• Patients must first demonstrate over 75% compliance with inhaled and/or oral corticosteroid therapy
• The asthma MDT and difficult asthma clinic normally assess patients between 18-80 years so only patients in this age range will be approached.
• All patients will be able to give informed consent for study participation.

You may not qualify if:

• Pregnancy
• Aged between 18-80 years old.
• Able to give informed consent
• Pregnancy
• Underlying respiratory conditions

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

Nottingham Respiratory BRU

Nottingham, NG51PB, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

1. Viral throat swab 2. Venous blood sampling: 40ml 3. Bronchoscopy: 20 mls bronchial wash, 4 bronchial brushes, 6 bronchial biopsies 4. Nasal brush 5. Passive saliva

MeSH Terms

Conditions

Asthma

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Central Study Contacts

Yik L Pang, BMedSci, MBBS, MRCP

CONTACT

01158231702; mszyp@exmail.nottingham.ac.uk

Mohammad R Ali, BSc, MRes

CONTACT

07812268393; mohammad.ali@nottingham.ac.uk

Study Design

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

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: October 3, 2019
• Study Start: December 31, 2018
• Primary Completion: June 30, 2021
• Study Completion: July 31, 2021
• Last Updated: November 3, 2020

Record last verified: 2020-11

Locations

GB (1)