AsthmaNCT00676572

p38 Mitogen-Activated Protein Kinase (MAPK) and Steroid Insensitivity in Asthma

An observational study of Asthma, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This research aims to find out how the inflammation in patients suffering from severe asthma is different from that in non-severe asthma, and how it may prevent corticosteroids from working efficiently in severe asthma. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Asthma
What is being tested?: Fiberoptic bronchoscopy; blood test
How many people: 12 participants
Where: 1 siteUnited Kingdom
Study dates: May 2008to Oct 2011
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
No healthy volunteers
Adult

Study population: Asthmatic subjects will be recruited from asthma clinics at the Royal Brompton Hospital and from primary care clinics.

Who may be able to join

Age 18-60
Physician diagnosis of asthma
Non-severe asthmatic subjects:
mild to moderately severe asthma.
The groups will be defined as follows, according to their need for treatments (as established in the Asthma Management GINA or BTS guidelines):
Mild: intermittent symptoms and need for reliever bronchodilator less than once a day

Show all 18Show fewer

moderate asthma: well-controlled asthma with minimal symptoms while on inhaled corticosteroid therapy not exceeding 2,000 μg beclomethasone equivalent.
Severe asthmatic subjects:
will have at least 1 major and 2 minor criteria (as below) Major characteristics (at least one of the following criteria)
Treatment with continuous or near continuous (>50% of year) oral corticosteroids
Requirement for treatment with high dose inhaled corticosteroids (ICS) Minor characteristics (at least 2 out of the following)
Requirement for daily treatment with a controller medication in addition to ICS e.g. LABA, theophylline, leukotriene antagonist
Asthma symptoms requiring SABA on a daily or near daily basis
Persistent airways obstruction (FEV1 <80% predicted, diurnal PEF variation >20%)
One or more emergency care visits for asthma per year
3 or more steroid "bursts" per year
Prompt deterioration with ≤ 25% reduction in oral or ICS
Near fatal asthma event in the past

Who cannot join

Current smokers, or less than 3 years since quitting smoking (< 5 pack/years)
Less than 4 weeks from an exacerbation
On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin
Concomitant anti-IgE therapy
On anti-platelet or anti-coagulant drugs
Low platelet count
Pregnancy or breast-feeding
Intubation for asthma within 6 months of entry into this study (if undergoing bronchoscopy)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Asthma Laboratory, Royal Brompton Hospital, Sydney Street
London, SW3 6NP

Other trials in United Kingdom

About this study

Official title: p38 MAPK Activation as the Basis for Corticosteroid Insensitivity in Severe Asthma

It will look,in particular, at a protein enzyme called p38 mitogen-activated protein kinase (p38 MAPK for short)which controls the activation of several important pathways in the cell. We wish to find out whether this enzyme is more active in cells obtained from patients with severe asthma compared to those with non-severe asthma. We would like to understand how this enzyme can cause the cell to respond less well to the anti-inflammatory effects of corticosteroids. We also wish to find out whether any specific inhibitors of p38 MAPK can improve severe asthma by improving the effects of corticosteroids on these cells.

We hypothesise that activation of the intracellular MAPK signalling pathway underlies the inflammatory processes of severe asthma, and leads to the diminution of the anti-inflammatory actions of CS through histone modification.

Read the detailed description

DESIGN Comparative study to analyse differences in the characteristics of lung macrophages and blood monocytes between non-severe and severe asthmatics.

AIMS

To determine whether there are differences in terms of cell expression and activation between lung macrophages and blood monocytes from non-severe and severe asthma
To determine the mechanisms of the lung macrophage and blood monocyte relative resistance to the effect of corticosteroids in severe asthma, and particularly focus on the role of p38 MAPK
To determine the differences in airway smooth muscle cells between non-severe and severe asthma

OUTCOME MEASURES

Clinically the differences in inflammatory and remodelling markers between non-severe and severe asthma
Differences in histone phosphorylation, NF-kB activity and glucocorticoid receptor activation and actions in macrophages and monocytes between non- severe and severe asthma
Differences in behaviour of airway smooth muscle cells cultured from biopsies obtained from non-severe and severe asthma

Severe and non-severe asthmatic subjects will be classified following ATS criteria. They undergo spirometry with reversibility testing, PC20, skin prick tests, exhaled nitric oxide measurements and induced sputum. They will have blood taken for PBMCs and undergo fiberoptic bronchoscopy for obtention of alveolar macrophages and bronchial biopsies

Conditions: Asthma
Being tested: Fiberoptic bronchoscopy; blood test
Keywords: severe asthma, corticosteroid insensitivity
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fiberoptic bronchoscopy; blood testOther
Fiberoptic bronchoscopy for obtention of alveolar macrophages and bronchial biopsies for histology and culture of airway smooth muscle cells

Study groups in NCT00676572
Study group	Role	What they receive
Severe asthma		Not described Receives: Other: Fiberoptic bronchoscopy; blood test
Non-severe asthma		Not described Receives: Other: Fiberoptic bronchoscopy; blood test

What is being measured

The primary outcome is the main question the study is designed to answer.

Differences in Activity and Downstream Activity of the p38 MAPK Activity in Macrophages or PBMCs Between Those From Severe and Non-Severe Asthmatics
Measured: 3 years

Secondary outcomes (1)

Differences in the Effect of p38 MAPK Inhibitor in Dexamethasone-Inhibition of Cytokine Release From Alveolar Macrophages and PBMCs Between Severe and Non-Severe Asthmatics
Percentage of Suppression of IL6 release by p38 MAPK inhibitor
Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Oct 2011

First posted13 May 2008 (estimated)
Study startMay 2008
Primary completionOct 2011
Study completionOct 2011

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: Other
Time perspective: Prospective
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00676572
Sponsor's protocol ID: 08/H0708/29
Other IDs: CRO1014
Status last verified: Oct 2019
First submitted: 8 May 2008
Last updated: 15 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

Bhavsar P, Khorasani N, Hew M, Johnson M, Chung KF. Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010 Apr;35(4):750-6. doi: 10.1183/09031936.00071309. Epub 2009 Oct 19.
PubMed 19840967

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: p38 MAPK Activation as the Basis for Corticosteroid Insensitivity in Severe Asthma
ClinicalTrials.gov ID: NCT00676572
Acronym / sponsor ID: 08/H0708/29
Conditions: Asthma
Keywords: severe asthma, corticosteroid insensitivity
Study type: Observational
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Collaborators: Royal Brompton & Harefield NHS Foundation Trust, Medical Research Council
Study start: May 2008 (actual)
Primary completion: Oct 2011 (actual)
Study completion: Oct 2011 (actual)
First posted: 13 May 2008 (estimated)
Results: Posted 4 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

DESIGN Comparative study to analyse differences in the characteristics of lung macrophages and blood monocytes between non-severe and severe asthmatics.

AIMS

To determine whether there are differences in terms of cell expression and activation between lung macrophages and blood monocytes from non-severe and severe asthma
To determine the mechanisms of the lung macrophage and blood monocyte relative resistance to the effect of corticosteroids in severe asthma, and particularly focus on the role of p38 MAPK
To determine the differences in airway smooth muscle cells between non-severe and severe asthma

OUTCOME MEASURES

Clinically the differences in inflammatory and remodelling markers between non-severe and severe asthma
Differences in histone phosphorylation, NF-kB activity and glucocorticoid receptor activation and actions in macrophages and monocytes between non- severe and severe asthma
Differences in behaviour of airway smooth muscle cells cultured from biopsies obtained from non-severe and severe asthma

Study design

Observational model: Other
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Severe asthma	–	Other: Fiberoptic bronchoscopy; blood test
Non-severe asthma	–	Other: Fiberoptic bronchoscopy; blood test

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult
Study population: Asthmatic subjects will be recruited from asthma clinics at the Royal Brompton Hospital and from primary care clinics.

Key inclusion criteria (18 listed)

Age 18-60
Physician diagnosis of asthma
mild to moderately severe asthma.
The groups will be defined as follows, according to their need for treatments (as established in the Asthma Management GINA or BTS guidelines):
will have at least 1 major and 2 minor criteria (as below) Major characteristics (at least one of the following criteria)

Key exclusion criteria (8 listed)

Current smokers, or less than 3 years since quitting smoking (< 5 pack/years)
Less than 4 weeks from an exacerbation
On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin
Concomitant anti-IgE therapy
On anti-platelet or anti-coagulant drugs

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
Fiberoptic bronchoscopy; blood testFiberoptic bronchoscopy for obtention of alveolar macrophages and bronchial biopsies for histology and culture of airway smooth muscle cells	Other	Non-severe asthma, Severe asthma

Primary outcome

Differences in Activity and Downstream Activity of the p38 MAPK Activity in Macrophages or PBMCs Between Those From Severe and Non-Severe Asthmatics
Time frame: 3 years

1 secondary outcome

Differences in the Effect of p38 MAPK Inhibitor in Dexamethasone-Inhibition of Cytokine Release From Alveolar Macrophages and PBMCs Between Severe and Non-Severe Asthmatics
Time frame: 3 years

Results and safety

Results posted to the registry on 4 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Severe Asthma	6	6
Non-severe Asthma	6	6

Primary outcome: Differences in Activity and Downstream Activity of the p38 MAPK Activity in Macrophages or PBMCs Between Those From Severe and Non-Severe Asthmatics

Time frame: 3 years

Population analysed: Data no collected

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 3 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Severe Asthma	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Non-severe Asthma	0 of 6 (0%)	0 of 6 (0%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19840967Bhavsar P, Khorasani N, Hew M, Johnson M, Chung KF. Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010 Apr;35(4):750-6. doi: 10.1183/09031936.00071309. Epub 2009 Oct 19.
Individual participant dataSharing planned: No

Related trials for Asthma

RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma

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

Pankaj Bhavsar, BSc PhD 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 18 inclusion and 8 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 15 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 4 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?

Differences in Activity and Downstream Activity of the p38 MAPK Activity in Macrophages or PBMCs Between Those From Severe and Non-Severe Asthmatics (time frame: 3 years). 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 NCT00676572, 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 15 Oct 2019.