Enhancement of in−Vitro GC Function in Patients With COPD
The global burden of COPD − a common and debilitating chronic inflammatory disease that is characterised by the progressive development of airflow limitation (shortness of breath − SOB) and is poorly reversible with currently available drugs −is increasing. Cigarette smoking is strongly linked with the ongoing inflammation; inflammation that can continue even when the patient has stopped smoking. The severity of airflow limitation (SOB) is correlated with the degree of pulmonary (lung) inflammation.
Histone deacetylases (HDACs)are important molecules in suppressing this pulmonary inflammation. We have recently shown that patients with COPD have a reduction in total HDAC which correlates with the severity of their lung disease.
Corticosteroids (anti−inflammatory treatment) act, at least in part, by recruitment of these HDACs to the site of active inflammatory gene transcription (which reduces the production of inflammatory molecules) and are widely used in COPD in patients with severe disease. Unfortunately, in COPD, inhaled corticosteroids seem to have little effect on the underlying inflammation (though in a selective group of patients with COPD they do reduce the number of infections a patient may have by a small amount). Theophylline has been used in the treatment of asthma and COPD for over 70 years, but its use has recently declined. Data so far obtained in primary cells (cells from patients used in the laboratory) from COPD patients suggests that low dose theophylline (~5mg/l) should be effective in restoring steroid sensitivity in patients with COPD (and hence reduce inflammation thus improving SOB). We wish therefore to continue these studies on theophylline principally by conducting a small clinical pilot study on 20−30 COPD patients in a randomised, double−blind, placebo−controlled, parallel−group study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Enhancement of in-Vitro GC Function in Patients With COPD. A Randomised, Double Blind, Placebo Controlled, Parallel-Group Study to Investigate the Effect of Theophylline and Fluticasone on Induced Sputum Cells Obtained Form COPD Patients|
- sputum inflammatory cell counts [ Time Frame: 4 weeks ]
|Study Start Date:||April 2006|
|Study Completion Date:||August 2007|
|Active Comparator: 1||
500 mg b.d.
|Placebo Comparator: 2||Drug: placebo|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00241631
|Windsor chest clinic KEVII Hospital|
|Windsor, Berks, United Kingdom, SL4 3DP|
|Principal Investigator:||ian adcock, PhD||Imperial College London|