A Proof of Concept Study to Evaluate the Dose Response for the Systemic Benefit Risk Ratio of Inhaled Fluticasone Propionate in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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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.

Official Title
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A Proof of Concept Study to Evaluate the Dose Response for the Systemic Benefit Risk Ratio of Inhaled Fluticasone Propionate in Chronic Obstructive Pulmonary Disease

Conditions
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COPD

Intervention / Treatment
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* Drug: Fluticasone propionate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled corticosteroid, Then placebo<br>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. After a washout period of 2 weeks, they then received FP matched placebo pMDI one puff twice daily for two weeks then FP four puffs twice daily for two weeks. | Drug: Fluticasone propionate<br> <br> Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo control, Then inhaled corticosteroid<br>FP matched placebo pMDI one puff twice daily for two weeks then FP four puffs twice daily for two weeks. After a washout period of 2 weeks, they then received 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. | Drug: Fluticasone propionate<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRP | C-reactive protein | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alveolar Nitric Oxide |  | 4 weeks | 
| OUCC | Overnight urinary cortisol creatinine ratio | 4 weeks |