Churg-Strauss SyndromeIDEANCT04671446
Identification of Autoantigens in EGPA and Severe Eosinophilic Asthma
An observational study of Churg-Strauss Syndrome and Eosinophilic Asthma, run by Queen Mary University of London at 2 sites in United Kingdom.
Trial summary
In this project the investigators will look for auto-antibodies to relevant proteins both in native form and importantly in post-translationally modified forms. Potential modified auto-antigens are eosinophil proteins (analogous to the cytoplasmic neutrophil proteins identified in vasculitides such as Granulomatosis… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Churg-Strauss Syndrome, Eosinophilic Asthma, Eosinophilic Esophagitis
- What is being tested?
- Autoantibody ELISA and Granulocyte Immunofluorescence
- How many people
- 120 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 10 Dec 2020to 5 May 2024
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients will be recruited via Outpatient Clinics conducted at St Bartholomew's (Bart's) Hospital, The Royal London Hospital, and Mile End Hospital (all Bart's Health NHS Trust), as well as from inpatients at these hospitals under the care of the Respiratory Medicine and Rheumatology teams (including those under other services needing inpatient respiratory medicine or rheumatology review).
Who may be able to join
- Severe Eosinophilic Asthma (with multi-disciplinary diagnosis as per ERS/ATS Criteria, blood eosinophils ≥ 0.3 x109/L on inhaled corticosteroids); or
- EGPA (as per American College of Rheumatology (ACR) Criteria); or
- Eosinophilic COPD (post-bronchodilator FEV1/FVC < 70% predicted, absence of bronchodilator reversibility, > 20 pack year smoking history, no history of asthma, blood eosinophils ≥ 0.3 x109/L); or
- Eosinophilic oesophagitis (with diagnostic histology); or
- Granulomatosis with Polyangiitis (GPA, formerly called Wegener's) (as per American College of Rheumatology (ACR) Criteria)
Who cannot join
- Known Pregnancy
- Anaemia
- Hepatitis B Virus, Hepatitis C Virus or HIV infection
- Donation of more than 240mls blood in the last sixteen weeks (four months) to any other research study or as a donation to the National Blood Transfusion Service
- Rituximab, plasmapharesis or polyclonal immunoglobulin infusion (ever)
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Barts Health NHS Trust, Dept of Rheumatology, Mile End Hospital
London, E1 4DG
Barts Health NHS Trust, Dept of Respiratory Medicine, St Bartholomew's Hospital
London, EC1A 7BE
About this study
Official title: Identification of Autoantigens and Their Potential Post-translational Modification in EGPA and Severe Eosinophilic Asthma
In this project the investigators will look for auto-antibodies to relevant proteins both in native form and importantly in post-translationally modified forms. Potential modified auto-antigens are eosinophil proteins (analogous to the cytoplasmic neutrophil proteins identified in vasculitides such as Granulomatosis with Polyangiitis (formerly known as Wegener's granulomatosis) and alternatively structural proteins such as collagen V. As well as advancing the understanding of asthma pathology, identifying a serum auto-antibody that could then be used as a clinical blood test, analogous to anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis, may revolutionise diagnosis of severe eosinophilic asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA). There is a considerable burden of undiagnosed severe eosinophilic asthma in part due to difficulties in definitive diagnosis and a diagnostic blood test would help diagnose these patients, allowing them to receive necessary treatment.
Read the detailed description
The investigators will approach the research question with parallel agnostic and targeted approaches.
In the agnostic approach the presence of auto-antibodies in patient serum and sputum to inactive and activated eosinophils, with and without post-translational modification, will be examined by indirect immunofluorescence.
In the targeted approach the investigators will examine by enzyme-linked immunoassay (ELISA) the presence/absence of antibodies to pre-selected candidate eosinophil and base membrane proteins both in native form and post-translationally modified. Proteins to examine will be chosen based on literature review (e.g. eosinophil peroxidase and collagen V) and eosinophil-specific proteins identified by FANTOM5 (Functional Annotation of the Mouse/Mammalian Genome) geneset analysis (FANTOM Consortium et al. 2014).
Both blood and sputum samples from highly-characterised patients with severe eosinophilic asthma and/or EGPA will be examined given the possibility of compartment-specific immune responses.
Once candidate auto-antigens have been identified in the selected group of patients with severe eosinophilic asthma and EGPA, the investigators will then examine their prevalence in serum samples from a wider selection of patients with eosinophilic airways diseases including mild-to-moderate asthma, severe eosinophilic asthma, EGPA, nasal polyposis and eosinophilic chronic obstructive pulmonary disease (COPD) as well as healthy controls. Length of disease, atopy, presence/absence nasal polyps, gender, age will be examined as co-variates. Correlations with highest blood eosinophil counts, requirement for oral corticosteroids and presence of other auto-antibodies, e.g. anti-MPO (myeloperoxidase) ANCA (anti-neutrophil cytoplasmic antibody), will be examined. In particular the investigators will look for the presence of novel autoantibodies in specific patient subsets: i) ANCA negative, ii) ANCA positive by immunofluorescence but negative for anti-MPO and anti-PR3 (proteinase-3) antibodies, iii) ANA (anti-nuclear antibody) positive but ANCA and extractable nuclear antigen (ENA) negative; since patients in all three groups may have novel, as yet undetermined autoantibodies. ROC (receiver operator characteristic curve) AUC (area under curve) analyses will be conducted to ascertain the predictive value of blood auto-antibodies for diagnosis of eosinophilic airways disease.
- Conditions
- Churg-Strauss Syndrome, Eosinophilic Asthma, Eosinophilic Esophagitis, Eosinophilic Pneumonia
- Being tested
- Autoantibody ELISA, Granulocyte Immunofluorescence
- Medical subject headings
- Churg-Strauss Syndrome, Pulmonary Eosinophilia, Eosinophilic Esophagitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autoantibody ELISADiagnostic test
Serum will be tested for novel autoantibodies against candidate auto-antigens by ELISA, such as those previously identified as of importance (e.g. eosinophil peroxidase, EPX) and also novel candidate proteins specific to eosinophils as identified by FANTOM5 geneset analysis.
Granulocyte ImmunofluorescenceDiagnostic test
The presence of auto-antibodies in patient serum to inactive and activated neutrophils / eosinophils, with and without post-translational modification, will be examined by indirect immunofluorescence.
| Study group | Role | What they receive |
|---|---|---|
| Severe eosinophilic asthma | Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma. Receives: Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence | |
| Other respiratory conditions | Milder asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis Receives: Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence | |
| Healthy controls | Healthy patients with no chronic lung condition. Receives: Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence | |
| EGPA | Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis) as per Wechsler et al. [N Engl J Med. 2017 May 18;376(20):1921-1932] Receives: Diagnostic Test: Autoantibody ELISA; Diagnostic Test: Granulocyte Immunofluorescence |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Percentage of Patients With a Positive Autoantibody ELISA
Serum tested for novel autoantibodies against candidate auto-antigens by ELISA. Outcome: Positive OD by ELISA (serum samples) to autoantigen panel (MPO, Collagen V, TREM1, IL1R2).
Measured: Baseline, at study entry
Secondary outcomes (1)
Number and Percentage of Patients With Positive Granulocyte Immunofluorescence
FITC anti-IgG immunofluorescence with slides of unstimulated/PMA-stimulated neutrophils (serum samples)
Measured: Baseline, at study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start10 Dec 2020
- Primary completion12 Oct 2022
- Study completion5 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Churg-Strauss SyndromeStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Myles J Lewis, MD PhD FRCP, Study chair, Queen Mary University of LondonPaul Pfeffer, MD, Principal investigator, Barts & The London NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04671446
- Sponsor's protocol ID
- IRAS 274097
- Other IDs
- 20/PR/0004
- Acronym
- IDEA
- Status last verified
- Dec 2024
- First submitted
- 26 Oct 2020
- Last updated
- 30 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Esposito I, Kontra I, Giacomassi C, Manou-Stathopoulou S, Brown J, Stratton R, Verykokou G, Buccafusca R, Stevens M, Nissim A, Lewis MJ, Pfeffer PE. Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma. Front Immunol. 2023 Jun 2;14:1164941. doi: 10.3389/fimmu.2023.1164941. eCollection 2023.
PubMed 37334358
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Autoantigens and Their Potential Post-translational Modification in EGPA and Severe Eosinophilic Asthma
- ClinicalTrials.gov ID
- NCT04671446
- Acronym / sponsor ID
- IDEA / IRAS 274097
- Conditions
- Churg-Strauss Syndrome, Eosinophilic Asthma, Eosinophilic Esophagitis, Eosinophilic Pneumonia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 12 Oct 2022 (actual)
- Study completion
- 5 May 2024 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Posted 30 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this project the investigators will look for auto-antibodies to relevant proteins both in native form and importantly in post-translationally modified forms. Potential modified auto-antigens are eosinophil proteins (analogous to the cytoplasmic neutrophil proteins identified in vasculitides such as Granulomatosis with Polyangiitis (formerly known as Wegener's granulomatosis) and alternatively structural proteins such as collagen V. As well as advancing the understanding of asthma pathology, identifying a serum auto-antibody that could then be used as a clinical blood test, analogous to anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis, may revolutionise diagnosis of severe eosinophilic asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA). There is a considerable burden of undiagnosed severe eosinophilic asthma in part due to difficulties in definitive diagnosis and a diagnostic blood test would help diagnose these patients, allowing them to receive necessary treatment.
Detailed description
The investigators will approach the research question with parallel agnostic and targeted approaches.
In the agnostic approach the presence of auto-antibodies in patient serum and sputum to inactive and activated eosinophils, with and without post-translational modification, will be examined by indirect immunofluorescence.
In the targeted approach the investigators will examine by enzyme-linked immunoassay (ELISA) the presence/absence of antibodies to pre-selected candidate eosinophil and base membrane proteins both in native form and post-translationally modified. Proteins to examine will be chosen based on literature review (e.g. eosinophil peroxidase and collagen V) and eosinophil-specific proteins identified by FANTOM5 (Functional Annotation of the Mouse/Mammalian Genome) geneset analysis (FANTOM Consortium et al. 2014).
Both blood and sputum samples from highly-characterised patients with severe eosinophilic asthma and/or EGPA will be examined given the possibility of compartment-specific immune responses.
Once candidate auto-antigens have been identified in the selected group of patients with severe eosinophilic asthma and EGPA, the investigators will then examine their prevalence in serum samples from a wider selection of patients with eosinophilic airways diseases including mild-to-moderate asthma, severe eosinophilic asthma, EGPA, nasal polyposis and eosinophilic chronic obstructive pulmonary disease (COPD) as well as healthy controls. Length of disease, atopy, presence/absence nasal polyps, gender, age will be examined as co-variates. Correlations with highest blood eosinophil counts, requirement for oral corticosteroids and presence of other auto-antibodies, e.g. anti-MPO (myeloperoxidase) ANCA (anti-neutrophil cytoplasmic antibody), will be examined. In particular the investigators will look for the presence of novel autoantibodies in specific patient subsets: i) ANCA negative, ii) ANCA positive by immunofluorescence but negative for anti-MPO and anti-PR3 (proteinase-3) antibodies, iii) ANA (anti-nuclear antibody) positive but ANCA and extractable nuclear antigen (ENA) negative; since patients in all three groups may have novel, as yet undetermined autoantibodies. ROC (receiver operator characteristic curve) AUC (area under curve) analyses will be conducted to ascertain the predictive value of blood auto-antibodies for diagnosis of eosinophilic airways disease.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Severe eosinophilic asthma | – | Diagnostic Test: Autoantibody ELISA, Diagnostic Test: Granulocyte ImmunofluorescencePatients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma. |
| Other respiratory conditions | – | Diagnostic Test: Autoantibody ELISA, Diagnostic Test: Granulocyte ImmunofluorescenceMilder asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis |
| Healthy controls | – | Diagnostic Test: Autoantibody ELISA, Diagnostic Test: Granulocyte ImmunofluorescenceHealthy patients with no chronic lung condition. |
| EGPA | – | Diagnostic Test: Autoantibody ELISA, Diagnostic Test: Granulocyte ImmunofluorescencePatients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis) as per Wechsler et al. [N Engl J Med. 2017 May 18;376(20):1921-1932] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients will be recruited via Outpatient Clinics conducted at St Bartholomew's (Bart's) Hospital, The Royal London Hospital, and Mile End Hospital (all Bart's Health NHS Trust), as well as from inpatients at these hospitals under the care of the Respiratory Medicine and Rheumatology teams (including those under other services needing inpatient respiratory medicine or rheumatology review).
Key inclusion criteria (5 listed)
- Severe Eosinophilic Asthma (with multi-disciplinary diagnosis as per ERS/ATS Criteria, blood eosinophils ≥ 0.3 x109/L on inhaled corticosteroids); or
- EGPA (as per American College of Rheumatology (ACR) Criteria); or
- Eosinophilic COPD (post-bronchodilator FEV1/FVC < 70% predicted, absence of bronchodilator reversibility, > 20 pack year smoking history, no history of asthma, blood eosinophils ≥ 0.3 x109/L); or
- Eosinophilic oesophagitis (with diagnostic histology); or
- Granulomatosis with Polyangiitis (GPA, formerly called Wegener's) (as per American College of Rheumatology (ACR) Criteria)
Key exclusion criteria (5 listed)
- Known Pregnancy
- Anaemia
- Hepatitis B Virus, Hepatitis C Virus or HIV infection
- Donation of more than 240mls blood in the last sixteen weeks (four months) to any other research study or as a donation to the National Blood Transfusion Service
- Rituximab, plasmapharesis or polyclonal immunoglobulin infusion (ever)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autoantibody ELISASerum will be tested for novel autoantibodies against candidate auto-antigens by ELISA, such as those previously identified as of importance (e.g. eosinophil peroxidase, EPX) and also novel candidate proteins specific to eosinophils as identified by FANTOM5 geneset analysis. | Diagnostic test | EGPA, Healthy controls, Other respiratory conditions, Severe eosinophilic asthma |
| Granulocyte ImmunofluorescenceThe presence of auto-antibodies in patient serum to inactive and activated neutrophils / eosinophils, with and without post-translational modification, will be examined by indirect immunofluorescence. | Diagnostic test | EGPA, Healthy controls, Other respiratory conditions, Severe eosinophilic asthma |
Primary outcome
Number and Percentage of Patients With a Positive Autoantibody ELISA
Time frame: Baseline, at study entry
Serum tested for novel autoantibodies against candidate auto-antigens by ELISA. Outcome: Positive OD by ELISA (serum samples) to autoantigen panel (MPO, Collagen V, TREM1, IL1R2).
1 secondary outcome
Number and Percentage of Patients With Positive Granulocyte Immunofluorescence
Time frame: Baseline, at study entry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37334358Esposito I, Kontra I, Giacomassi C, Manou-Stathopoulou S, Brown J, Stratton R, Verykokou G, Buccafusca R, Stevens M, Nissim A, Lewis MJ, Pfeffer PE. Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma. Front Immunol. 2023 Jun 2;14:1164941. doi: 10.3389/fimmu.2023.1164941. eCollection 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Myles J Lewis, MD PhD FRCP study chair
Queen Mary University of London
Paul Pfeffer, MD principal investigator
Barts & The London NHS Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Churg-Strauss Syndrome and Eosinophilic Asthma, run by Queen Mary University of London at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and Percentage of Patients With a Positive Autoantibody ELISA (time frame: Baseline, at study entry). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04671446, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.