AsthmaNCT02660853
Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers
A study testing FEV1 in people with Asthma, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The purpose of this study is to investigate exacerbations in severe asthma with regard to symptoms, lung function, aetiology and biomarkers. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Asthma
- What is being tested?
- FEV1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2015to Jun 2017
- Phase
- Interventional
- 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 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients must be able to give informed consent. The definition of severe asthma will be on the basis of
- Uncontrolled asthma: three or more of the following features present in any week in the previous 4 weeks:
- Daytime symptoms more than twice per week
- Any limitation of activities
- Nocturnal symptoms once or more per week
- Need for reliever treatment more than twice per week
Show all 9Show fewer
- Pre bronchodilator FEV1 <80% predicted or personal best OR
- Frequent severe exacerbations (≥2 per year) OR
- Require prescription of daily or alternate day oral corticosteroids (OCS) to achieve asthma control despite the prescription of high dose inhaled corticosteroids (>1000mcg fluticasone propionate daily or equivalent) or maintenance oral corticosteroids plus a long acting beta agonist or one other controller medication (for example anti-cholinergics, leukotriene receptor antagonists or theophylline).
Who cannot join
- • Current smoker, or Ex-smoker with a >10 year pack history or having smoked within the past 6 months
- Significant alternative diagnoses that may mimic or complicate asthma, in particular dysfunctional breathing, panic attacks, and overt psychosocial problems (if these are thought to be the major problem rather than in addition to severe asthma)
- Significant other primary pulmonary disorders in particular pulmonary embolism, pulmonary hypertension, interstitial lung disease and lung cancer
- Subjects with emphysema and bronchiectasis should only be excluded if this is thought to be the major pulmonary disorder rather than in addition to severe asthma
- Diagnosis or current investigation of occupational asthma
- Any subjects currently participating, or having participated within 3 months of the first dose in a study using a new molecular entity, or the first dose in any other study investigating drugs.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Biomedical research Unit, Royal Brompton Hospital, Sydney Street
London, SW3 6NP
About this study
The purpose of this study is to investigate exacerbations in severe asthma with regard to symptoms, lung function, aetiology and biomarkers.
Read the detailed description
Patients will be recruited from the Severe Asthma Clinics at Royal Brompton Hospital. At the first visit the investigators will enrol and characterise patients. This will involve asking patients to keep a diary record of PEFR(Peak Expiratory Flow Rate), spirometry, symptom scores, use of beta-agonist reliever and other treatments for 2 weeks. Bloods tests will be taken for markers of systemic inflammation. Markers of oxidative stress will be measured in blood, exhaled breath condensate (EBC) and urine: malondialdehyde (MDA) and 8-isoprostanes. Nitric oxide (NO) levels in exhaled breath will be measured measured twice daily for 2 weeks using a portable hand-held NO meter. If spontaneous sputum is not available, sputum will be induced using ultrasonic nebulization of isotonic saline. Profile of inflammatory cells, cytokines in supernatants, bacteriological culture and microbiome analysis will be measured in the sputum. Patients will be observed over 12 months during which time the number of exacerbations will be recorded on basis of objective measures with evaluation of ACQ (Asthma Control Questionnaire), daily morning and evening PEF (Peak Expiratory Flow). At the earliest onset of exacerbation, the patient will be requested to contact the Asthma Research Unit. Patients will then be asked to attend the laboratory where similar tests to the first visit will be performed. For other exacerbations not studied, the patient will be asked to keep a detailed diary record of symptoms with severity scoring and spirometric and PEF measurements (Exacerbation Diary) over a period of 2 weeks after onset of exacerbation.
As patients with severe asthma are usually very well experienced in what the symptoms of exacerbations are, they will therefore be asked to recognise their own exacerbations. Each patient has their own way of recognising an exacerbation and the investigators will discuss this with each patient and try and establish whether an earlier warning signal is possible. Patients will be asked to record their symptoms and lung function as soon as they feel the onset of an exacerbation, since exacerbations are recognised by the patient as events that are 'clinically identified by being outside the patient's usual range of day-to-day variation'. The patient will receive or administer treatments for the exacerbation as usual without interference from the Research Team except for starting any antibiotic therapies, which will be started (if prescribed) as soon as the visit studies have been completed. Those who have been hospitalized will not be studied, and only those who can attend the Clinical Research Unit will be studied.
- Conditions
- Asthma
- Being tested
- FEV1
- Keywords
- Exacerbations
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FEV1Diagnostic test
Participants have FEV1 test
| Study group | Role | What they receive |
|---|---|---|
| Severe Asthma | Other | Patients under Steps 4/5 of Asthma Treatment - SIGN (Scottish Intercollegiate Guidelines Network) / BTS (British Thoracic Society) Guidelines Receives: Diagnostic Test: FEV1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Predicted FEV1
From date of screening visit until date of first asthma exacerbation visit Percent predicted Forced Expiratory Volume in First Second
Measured: Baseline Visit, 12 months
Secondary outcomes (9)
Exhaled Breath Condensate
pH and free Iron
Measured: Baseline Visit, 12 months
Markers of Oxidative Stress in Urine
malondialdehyde (MDA)
Measured: Baseline Visit, 12 months
Markers of Oxidative Stress in Urine
8-isoprostanes
Measured: Baseline Visit, 12 months
Sputum Analysis
Eosinophils as percentage of total count
Measured: From baseline visit and 12 months
PCR for Respiratory Viruses
nasopharyngeal swabs
Measured: Baseline Visit, 12 months
Sputum Microbiome
Measured: Baseline Visit, 12 months
Corticosteroid Insensitivity in Peripheral Blood Mononuclear Cells
Measured: Baseline Visit, 12 months
Exhaled Nitric Oxide
Measured: Baseline Visit, 12 months
Exhaled Hydrogen Sulphide
Measured: Baseline Visit, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2016 (estimated)
- Study startJun 2015
- Primary completionJun 2017
- Study completionJun 2017
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.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Imperial College 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Kian F Chung, MBBS MD FRCP, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02660853
- Sponsor's protocol ID
- 13/LO/1198
- Status last verified
- Nov 2019
- First submitted
- 2 Nov 2015
- Last updated
- 3 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers
- ClinicalTrials.gov ID
- NCT02660853
- Acronym / sponsor ID
- 13/LO/1198
- Conditions
- Asthma
- Keywords
- Exacerbations
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Study start
- Jun 2015
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 21 Jan 2016 (estimated)
- Results
- Posted 31 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate exacerbations in severe asthma with regard to symptoms, lung function, aetiology and biomarkers.
Detailed description
Patients will be recruited from the Severe Asthma Clinics at Royal Brompton Hospital. At the first visit the investigators will enrol and characterise patients. This will involve asking patients to keep a diary record of PEFR(Peak Expiratory Flow Rate), spirometry, symptom scores, use of beta-agonist reliever and other treatments for 2 weeks. Bloods tests will be taken for markers of systemic inflammation. Markers of oxidative stress will be measured in blood, exhaled breath condensate (EBC) and urine: malondialdehyde (MDA) and 8-isoprostanes. Nitric oxide (NO) levels in exhaled breath will be measured measured twice daily for 2 weeks using a portable hand-held NO meter. If spontaneous sputum is not available, sputum will be induced using ultrasonic nebulization of isotonic saline. Profile of inflammatory cells, cytokines in supernatants, bacteriological culture and microbiome analysis will be measured in the sputum. Patients will be observed over 12 months during which time the number of exacerbations will be recorded on basis of objective measures with evaluation of ACQ (Asthma Control Questionnaire), daily morning and evening PEF (Peak Expiratory Flow). At the earliest onset of exacerbation, the patient will be requested to contact the Asthma Research Unit. Patients will then be asked to attend the laboratory where similar tests to the first visit will be performed. For other exacerbations not studied, the patient will be asked to keep a detailed diary record of symptoms with severity scoring and spirometric and PEF measurements (Exacerbation Diary) over a period of 2 weeks after onset of exacerbation.
As patients with severe asthma are usually very well experienced in what the symptoms of exacerbations are, they will therefore be asked to recognise their own exacerbations. Each patient has their own way of recognising an exacerbation and the investigators will discuss this with each patient and try and establish whether an earlier warning signal is possible. Patients will be asked to record their symptoms and lung function as soon as they feel the onset of an exacerbation, since exacerbations are recognised by the patient as events that are 'clinically identified by being outside the patient's usual range of day-to-day variation'. The patient will receive or administer treatments for the exacerbation as usual without interference from the Research Team except for starting any antibiotic therapies, which will be started (if prescribed) as soon as the visit studies have been completed. Those who have been hospitalized will not be studied, and only those who can attend the Clinical Research Unit will be studied.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Severe Asthma | Other | Diagnostic Test: FEV1Patients under Steps 4/5 of Asthma Treatment - SIGN (Scottish Intercollegiate Guidelines Network) / BTS (British Thoracic Society) Guidelines |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- All patients must be able to give informed consent. The definition of severe asthma will be on the basis of
Key exclusion criteria (6 listed)
- • Current smoker, or Ex-smoker with a >10 year pack history or having smoked within the past 6 months
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 |
|---|---|---|
| FEV1Participants have FEV1 test | Diagnostic test | Severe Asthma |
Primary outcome
Percent Predicted FEV1
Time frame: Baseline Visit, 12 months
From date of screening visit until date of first asthma exacerbation visit Percent predicted Forced Expiratory Volume in First Second
9 secondary outcomes
Exhaled Breath Condensate
Time frame: Baseline Visit, 12 months
Markers of Oxidative Stress in Urine
Time frame: Baseline Visit, 12 months
Markers of Oxidative Stress in Urine
Time frame: Baseline Visit, 12 months
Sputum Analysis
Time frame: From baseline visit and 12 months
PCR for Respiratory Viruses
Time frame: Baseline Visit, 12 months
Sputum Microbiome
Time frame: Baseline Visit, 12 months
Corticosteroid Insensitivity in Peripheral Blood Mononuclear Cells
Time frame: Baseline Visit, 12 months
Exhaled Nitric Oxide
Time frame: Baseline Visit, 12 months
Exhaled Hydrogen Sulphide
Time frame: Baseline Visit, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Kian F Chung, MBBS MD FRCP principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FEV1 in people with Asthma, run by Imperial College London at 1 site 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 9 inclusion and 6 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 3 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 31 Oct 2019). 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?
Percent Predicted FEV1 (time frame: Baseline Visit, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Dec 2019.