None listed
Conditions
Brief summary
1. The first hypothesis is that non-eosinophilic asthma is steroid resistant 2. The second hypothesis is that non-eosinophilic asthma will respond to one or more of the currently available anti-inflammatory agents i.e. clarithromycin, theophylline, formoterol 1. To identify patients with non-eosinophilic asthma from the research database of the Otago Respiratory Research Unit. This will involve a clinical assessment, a standard four-week period of inhaled steroid withdrawal, followed by a hypertonic saline challenge and induced sputum analysis to document the presence of airway hyper-responsiveness and eosinophilic / non-eosinophilic asthma. 2. To confirm the relationship between inflammatory cell type and steroid responsiveness 3. To undertake a randomized controlled trial of three currently available asthma treatments: formoterol, theophylline, and clarithromycin.
Interventions
The study will comprise three Phases:
Phase 1: Steroid withdrawal for 28 days (or less, if loss of control occurs). This has been undertaken frequently in previous studies for which Ethics Approval has been received. This permits the true “naïve” asthma state to be characterised (eosinophilic or non-eosinophilic) using a combined hypertonic saline challenge (via a nebuliser) and induced sputum analysis. Airway hyper-responsiveness (AHR) to adenosine monophosphate (AMP) will also be assessed. AMP
The study will comprise three Phases: Phase 1: Steroid withdrawal for 28 days (or less, if loss of control occurs). This has been undertaken frequently in previous studies for which Ethics Approval has been received. This permits the true “naïve” asthma state to be characterised (eosinophilic or non-eosinophilic) using a combined hypertonic saline challenge (via a nebuliser) and induced sputum analysis. Airway hyper-responsiveness (AHR) to adenosine monophosphate (AMP) will also be assessed. AMP challenge is the most sensitive objective measure for steroid response. The procedures have been routinely used in research studies over the last 10 years. Patients with sputum eosinophil count of less than 2% AND objective evidence of AHR will be allocated to Group A. Patients with sputum eosinophil count of greater than 2% will be allocated to Group B. Phase 2: Trial of steroid. Forty patients in Group A and the first 40 patients in group B will undergo a fixed-order, double-blind, placebo-controlled trial of inhaled fluticasone 1000µg/day followed by matching placebo. Each treatment period will be for 21 days. At the end of each of the two treatment periods, a combined hypertonic saline challenge and induced sputum analysis, as well as AMP challenge will be undertaken. Data from these tests will be used to identify individual steroid responsiveness as well as between-group differences. This will confirm the premise that non-eosinophilic asthma is NOT steroid responsive. Phase 3: Cross-over trial of alternative therapies. Patients in group A who are not steroid responsive will then enter a year-long randomised-order, double-blind, placebo-controlled, cross-over trial of inhaled formoterol (12µg b.i.d.), oral theophylline (300 mg. b.i.d.), and oral clarithromycin (250 mg. b.i.d.). Matching tablets and inhalers will be used to maintain blinding. Each treatment will be given for three months. Data for the first two weeks of each treatment period will be ignored (washout).
Sponsors
University of Otago, Dunedin, New Zealand
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Moderately severe chronic persistent asthma.
Exclusion criteria
History of life-threatening asthma episodes, current smoker, pregnant or likely to become pregnant.
Outcome results
None listed