Asthma Respiratory Asthma
Conditions
Interventions
The study population will be screened including medical history, examination, spirometry, diary card monitoring, exhaled nitric oxide measurement, skinprick testing, mannitol and metacholine provocati
Sponsors
Southampton University Hospitals NHS Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 - 50 years, either gender 2. Confirmed diagnosis of asthma for greater than 1 year as defined by British Thoracic Society (BTS) guidelines, requiring treatment with high dose inhaled corticosteroids in combination with long acting beta-2-agonists, with persisting symptoms requiring use of short-acting beta agonist therapy greater than 3 x/week 3. Lifelong non-smoker 4. Forced expiratory volume in one second (FEV1) greater than 40% 5. Subject must understand the procedures of the study and agree to participation in the study by providing written informed consent 6. Subject considered fit enough to undergo lung function testing including provocation tests, and bronchoscopy 7. Subject must not be participating in another clinical trial or have done so within the last 12 weeks
Exclusion criteria
Exclusion criteria: 1. Pregnancy (where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin [hCG] laboratory test greater than 5 mIU/ml), an intention to become pregnant or breast-feeding (lactating) 2. Subjects with active lung disease other than asthma 3. Significant medical (cardiopulmonary, neurological, renal, endocrine, gastrointestinal, psychiatric, hepatic or haematological) co-morbidity which in the view of the investigator could impact on the interpretation of results or participation in the trial, or which is uncontrolled with standard treatment 4. Current participation in another clinical trial or previous participation within the last 12 weeks 5. Alcohol or active drug abuse 6. Ongoing allergen desensitisation therapy 7. Regular use of sedatives, hypnotics, tranquilisers 8. Cancer or previous history of cancer 9. Inability to understand directions for dosing and study assessment 10. Inability to be contacted in case of emergency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in provocative concentration in mannitol causing a 20% fall in FEV1 (PC20), measured in screening and on days 3, 14, 18 and 36 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Asthma symptoms, assessed continuously during the trial 2. Short acting B-2-agonist usage, assessed continuously during the trial 3. Lung function (home peak expiratory flow rate [PEFR] recording and clinic FEV1 and forced vital capacity [FVC]) 4. Change in PC20 methacholine, assessed in screening and on day 17 and 35 5. Change in exhaled NO (eNO), assessed in screening and on days 3, 14, 18 and 36 6. Expression of ZO-1 and occludin in the bronchial epithelium 7. Bronchial biopsy epithelial integrity 8. Mucosal cellular inflammation (eosinophils, mast cells, neutrophils T-cells), assessed from bronchocopy in screening and on day 21 9. Epithelial activation markers (interleukin-8 [IL-8], regulated upon activation, normal T cell expressed and secreted [RANTES], macrophage inflammatory protein-1alpha [MIP-1a], macrophage chemotactic protein-1 [MCP-1], transforming growth factor alpha [TGF-a], epidermal growth factor receptor [EGFR]), assessed from bronchocopy in screening and on day 21 10. Safety readouts (clinical adverse event reporting), assessed continuously 11. Safety-related histochemistry readouts (epithelial Ki 61), assessed continuously | — |
Countries
United Kingdom
Outcome results
None listed