AsthmaNCT00779870
Airway Smooth Muscle and Asthma Severity
An observational study of Asthma, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Our hypothesis is that the severity of asthma is determined by the way in which airway smooth muscle cells grow and release inflammatory mediators. Our main objective is to establish how the properties of the airway smooth muscle cell varies with asthma severity. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- bronchoscopy
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2008to Sep 2012
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Mild, moderate and severe asthmatics, with a control group of healthy non-smoking volunteers
Who may be able to join
- Age 18 - 60 Non smokers (or less than 5 pack/yrs if ex-smokers) Normal lung function
Who cannot join
- History of asthma or allergic rhinitis Any chronic illness Current smokers, or less than 3 years since quitting smoking (< 5 pack/years) PC20 less than 16mg/ml On anti-platelet or anti-coagulant drugs Low platelet count Pregnancy or breast-feeding Previous bronchoscopy within three months of this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Role of Oxidant/Anti-oxidant Balance and the Relationship of Asthma Severity on Airway Smooth Muscle Proliferation, Migration and Cytokine Release.
Our hypothesis is that the severity of asthma is determined by the way in which airway smooth muscle cells grow and release inflammatory mediators. Our main objective is to establish how the properties of the airway smooth muscle cell varies with asthma severity. Environmental agents, such as cigarette smoke, and inflammation can give rise to oxidative stress - this is a process whereby harmful chemicals called free radicals are formed in the body and damage tissues. The damage caused can be limited/prevented by protective, or anti-oxidant mediators. We will also look at molecules involved in oxidative stress which may affect the way in which the airway smooth muscle grows and produces inflammatory mediators.
Read the detailed description
Aims and Objectives The objective of this study is to examine whether the severity of asthma is related to (and possibly caused by) ASM dysfunction. Severe asthmatics have been shown to have more ASM in bronchial biopsies than non-severe asthmatics16. Because ASM cells can be obtained from bronchial biopsies obtained via bronchoscopy, we will examine endobronchial biopsies from mild, moderate and severe asthmatics, and healthy non-asthmatic subjects to compare features of remodelling (severe asthmatic subjects will have been assessed through the Difficult Asthma Protocol at the Royal Brompton Hospital24). In particular, we will focus on ASM mass, proliferation and changes in expression of different contractile proteins (α-actin and myosin) and chemokines, and will assess in vitro the response of ASM cells to stimulation by TGF-β and IL-1β. We will also examine the effect of dexamethasone on chemokine release and induced proliferation in vitro. We will also study enzymes and anti-oxidants involved in oxidative stress, such as Nox4, MnSOD and catalase, to look at their role in regulating ASM cell proliferation and chemokine synthesis. We want to see if there is an oxidant-anti oxidant balance in ASM in severe asthma compared to non-severe asthma.
AIM:
- To establish the difference in ASM phenotype in asthma patients of differing severity of disease in terms of ASM mass, proliferation, migration and chemokine release.
Study design There will be 3 study visits. In the first two visits, the subjects will undergo spirometry with reversibility testing, a methacholine challenge test (to assess degree of bronchial hyper-responsiveness), skin prick tests and IgE levels (to assess atopic status), measurement of exhaled nitric oxide (as a non-invasive marker of inflammation), and the asthmatic subjects will complete an Asthma Control Questionnaire and an Asthma Quality of Life Questionnaire. The third visit will be on the day admission for the bronchoscopy.
Study protocol:
Visit 1 - screening visit
- Explain purpose of study- address any queries/concerns
- History and examination
- Skin prick tests
- Blood test for full blood count, clotting profile and IgE
- Measurement of exhaled nitric oxide (eNO)
- Spirometry pre and post β agonist
- Completion of Asthma Control Questionnaire and
- Completion of Asthma Quality of Life Questionnaire
Visit 2 - Methacholine challenge test
Visit 3 - Day admission for fibreoptic bronchoscopy
- Conditions
- Asthma
- Being tested
- bronchoscopy
- Keywords
- asthma severity, airway smooth muscle, oxidative stress
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bronchoscopyOther
bronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies
| Study group | Role | What they receive |
|---|---|---|
| 1 | healthy volunteers Receives: Other: bronchoscopy | |
| 2 | mild asthmatics Receives: Other: bronchoscopy | |
| 3 | moderately-severe asthmatics Receives: Other: bronchoscopy | |
| 4 | severe asthmatics Receives: Other: bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in ASM Mass Between Groups
Measured: at time of bronchoscopy, an average of 1 hour
Difference in ASM Proliferation, Migration and Cytokine Release Between Groups
Measured: at time of bronchoscopy, an average of 1 hour
Difference in Intracellular Oxidative Stress Mechanisms From ASM Between Groups
Expression of Nrf2 protein
Measured: at time of bronchoscopy, an average of 1 hour
Secondary outcomes (1)
Correlation Between ASM Mass and Airway Hyper-responsiveness (PC20)
Measured: at the time of bronchoscopy, an average of 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionSep 2012
- Study completionSep 2012
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 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Asthma UK, Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Principal investigator, Fan Chung, Imperial College London
- Investigators
- Kian F Chung, MBBS MD FRCP DSc, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00779870
- Sponsor's protocol ID
- 08/H0708/2
- Status last verified
- Oct 2019
- First submitted
- 22 Oct 2008
- Last updated
- 31 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Michaeloudes C, Chang PJ, Petrou M, Chung KF. Transforming growth factor-beta and nuclear factor E2-related factor 2 regulate antioxidant responses in airway smooth muscle cells: role in asthma. Am J Respir Crit Care Med. 2011 Oct 15;184(8):894-903. doi: 10.1164/rccm.201011-1780OC.
PubMed 21799075
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Role of Oxidant/Anti-oxidant Balance and the Relationship of Asthma Severity on Airway Smooth Muscle Proliferation, Migration and Cytokine Release.
- ClinicalTrials.gov ID
- NCT00779870
- Acronym / sponsor ID
- 08/H0708/2
- Conditions
- Asthma
- Keywords
- asthma severity, airway smooth muscle, oxidative stress
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Asthma UK, Royal Brompton & Harefield NHS Foundation Trust
- Study start
- Oct 2008 (actual)
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 24 Oct 2008 (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.
Our hypothesis is that the severity of asthma is determined by the way in which airway smooth muscle cells grow and release inflammatory mediators. Our main objective is to establish how the properties of the airway smooth muscle cell varies with asthma severity. Environmental agents, such as cigarette smoke, and inflammation can give rise to oxidative stress - this is a process whereby harmful chemicals called free radicals are formed in the body and damage tissues. The damage caused can be limited/prevented by protective, or anti-oxidant mediators. We will also look at molecules involved in oxidative stress which may affect the way in which the airway smooth muscle grows and produces inflammatory mediators.
Detailed description
Aims and Objectives The objective of this study is to examine whether the severity of asthma is related to (and possibly caused by) ASM dysfunction. Severe asthmatics have been shown to have more ASM in bronchial biopsies than non-severe asthmatics16. Because ASM cells can be obtained from bronchial biopsies obtained via bronchoscopy, we will examine endobronchial biopsies from mild, moderate and severe asthmatics, and healthy non-asthmatic subjects to compare features of remodelling (severe asthmatic subjects will have been assessed through the Difficult Asthma Protocol at the Royal Brompton Hospital24). In particular, we will focus on ASM mass, proliferation and changes in expression of different contractile proteins (α-actin and myosin) and chemokines, and will assess in vitro the response of ASM cells to stimulation by TGF-β and IL-1β. We will also examine the effect of dexamethasone on chemokine release and induced proliferation in vitro. We will also study enzymes and anti-oxidants involved in oxidative stress, such as Nox4, MnSOD and catalase, to look at their role in regulating ASM cell proliferation and chemokine synthesis. We want to see if there is an oxidant-anti oxidant balance in ASM in severe asthma compared to non-severe asthma.
AIM:
- To establish the difference in ASM phenotype in asthma patients of differing severity of disease in terms of ASM mass, proliferation, migration and chemokine release.
Study design There will be 3 study visits. In the first two visits, the subjects will undergo spirometry with reversibility testing, a methacholine challenge test (to assess degree of bronchial hyper-responsiveness), skin prick tests and IgE levels (to assess atopic status), measurement of exhaled nitric oxide (as a non-invasive marker of inflammation), and the asthmatic subjects will complete an Asthma Control Questionnaire and an Asthma Quality of Life Questionnaire. The third visit will be on the day admission for the bronchoscopy.
Study protocol:
Visit 1 - screening visit
- Explain purpose of study- address any queries/concerns
- History and examination
- Skin prick tests
- Blood test for full blood count, clotting profile and IgE
- Measurement of exhaled nitric oxide (eNO)
- Spirometry pre and post β agonist
- Completion of Asthma Control Questionnaire and
- Completion of Asthma Quality of Life Questionnaire
Visit 2 - Methacholine challenge test
Visit 3 - Day admission for fibreoptic bronchoscopy
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Other: bronchoscopyhealthy volunteers |
| 2 | – | Other: bronchoscopymild asthmatics |
| 3 | – | Other: bronchoscopymoderately-severe asthmatics |
| 4 | – | Other: bronchoscopysevere asthmatics |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Mild, moderate and severe asthmatics, with a control group of healthy non-smoking volunteers
Key inclusion criteria (1 listed)
- Age 18 - 60 Non smokers (or less than 5 pack/yrs if ex-smokers) Normal lung function
Key exclusion criteria (1 listed)
- History of asthma or allergic rhinitis Any chronic illness Current smokers, or less than 3 years since quitting smoking (< 5 pack/years) PC20 less than 16mg/ml On anti-platelet or anti-coagulant drugs Low platelet count Pregnancy or breast-feeding Previous bronchoscopy within three months of this study
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 |
|---|---|---|
| bronchoscopybronchoscopy under local anaesthetic and sedation to obtain endobronchial biopsies | Other | 1, 2, 3, 4 |
Primary outcome
Difference in ASM Mass Between Groups
Time frame: at time of bronchoscopy, an average of 1 hour
Difference in ASM Proliferation, Migration and Cytokine Release Between Groups
Time frame: at time of bronchoscopy, an average of 1 hour
Difference in Intracellular Oxidative Stress Mechanisms From ASM Between Groups
Time frame: at time of bronchoscopy, an average of 1 hour
Expression of Nrf2 protein
1 secondary outcome
Correlation Between ASM Mass and Airway Hyper-responsiveness (PC20)
Time frame: at the time of bronchoscopy, an average of 1 hour
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21799075Michaeloudes C, Chang PJ, Petrou M, Chung KF. Transforming growth factor-beta and nuclear factor E2-related factor 2 regulate antioxidant responses in airway smooth muscle cells: role in asthma. Am J Respir Crit Care Med. 2011 Oct 15;184(8):894-903. doi: 10.1164/rccm.201011-1780OC.
- 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 DSc 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?
An observational study of 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 1 inclusion and 1 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 31 Oct 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?
Difference in ASM Mass Between Groups (time frame: at time of bronchoscopy, an average of 1 hour). The study lists 3 primary outcomes in all. 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 NCT00779870, 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 31 Oct 2019.