COPD
Conditions
Brief summary
Chronic Obstructive Pulmonary Disease (COPD) is a major worldwide problem.Steroids inhalers are now an established treatment for COPD. Inhaled steroids can have a number of bad effects including suppression of the adrenal glands because of absorption. A previous study in patients with COPD. C-reactive Protein (CRP) is a peptide produced in the liver in response to inflammation. Elevated circulating levels of CRP are associated with heart conditions. High levels of CRP have also been found in patients with COPD. In some studies, steroid inhalers have reduced CRP levels, and that of other inflammatory mediators, in patients with COPD. It is unknown whether this reflects a reduction in lung inflammation or an effect of systemically absorbed corticosteroid. It is proposed to investigate the link between inhaled corticosteroid and serum CRP, lung inflammation (measured by exhaled nitric oxide) and systemic absorption of steroids.
Interventions
DRUGFluticasone propionate
DRUGPlacebo
Sponsors
University of Dundee
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Current or ex-smokers * Aged over 50years * FEV1/FVC ratio \<0.7 * FEV1\<80% predicted * Improvement in FEV1 following short acting beta-agonist not greater than 15% and 200ml.
Exclusion criteria
* Diagnosis of asthma, bronchiectasis or ABPA * Inability to perform study procedures or give informed consent * Known sensitivity to trial medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CRP | 4 weeks | C-reactive protein |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alveolar Nitric Oxide | 4 weeks | — |
| OUCC | 4 weeks | Overnight urinary cortisol creatinine ratio |
Participant flow
Pre-assignment details
This is a randomised, double blind placebo controlled cross over trial design will be used. Following a two-week steroid tapering process and a two-week run in period, two randomised treatment periods will follow. Each will be one month in duration and will be separated by a two-week wash-out period.
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Corticosteroid, Then Placebo or Vice Versa FP 250μg per actuation pMDI one puff twice daily (total daily dose 500μg) for two weeks then FP 250μg per actuation pMDI four puffs twice daily (total daily dose 2000μg) for two weeks.
Then 2 weeks of wash-out.
Then followed by FP matched placebo pMDI one puff twice daily for two weeks then FP four puffs twice daily for two weeks. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Inhaled Corticosteroid, Then Placebo or Vice Versa |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Region of Enrollment United Kingdom | 18 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
CRP
C-reactive protein
Time frame: 4 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inhaled Corticosteroid | CRP | 2.9 mg/L |
| Placebo Control | CRP | 2.0 mg/L |
Secondary
Alveolar Nitric Oxide
Time frame: 4 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inhaled Corticosteroid | Alveolar Nitric Oxide | 1.7 ppb |
| Placebo Control | Alveolar Nitric Oxide | 3.1 ppb |
Secondary
OUCC
Overnight urinary cortisol creatinine ratio
Time frame: 4 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inhaled Corticosteroid | OUCC | 2.7 nmol/mmol |
| Placebo Control | OUCC | 8.8 nmol/mmol |