N/A
N=12
p38 Mitogen-Activated Protein Kinase (MAPK) and Steroid Insensitivity in Asthma
Asthma
Bottom Line
View on ClinicalTrials.gov: NCT00676572 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Oct 2019
Primary outcome: Primary: Differences in Activity and Downstream Activity of the p38 MAPK Activity in Macrophages or PBMCs Between Those From Severe and Non-Severe Asthmatics
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Fiberoptic bronchoscopy; blood test (Other)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Imperial College London
- Primary completion
- Oct 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Differences in Activity and Downstream Activity of the p38 MAPK Activity in Macrophages or PBMCs Between Those From Severe and Non-Severe Asthmatics |
— | — |
| SECONDARY 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 |
50; 8 | <0.05 sig |
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.
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.
Eligibility Criteria
Inclusion Criteria
- 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
- 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 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
Exclusion Criteria
- 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)
Data sourced from ClinicalTrials.gov (NCT00676572). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.