NCT00119496

Rosiglitazone Versus Theophylline in Asthmatic Smokers

A Clinical Study to Investigate the Effect of Rosiglitazone, Theophylline and Inhaled Corticosteroid, Inflammation and Pulmonary Function in Asthmatic Smokers

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 79 (actual)
• Sponsor: University of Glasgow · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Asthmatic smokers display a blunted response to both inhaled and oral corticosteroid treatments and are at increased risk for exacerbations and near fatal asthma. The prevalence of smoking in asthmatics runs between 20-30%. Therefore, new, more efficacious treatments are required. Recent work has demonstrated a mechanism which may explain steroid resistance. A commonly used drug called theophylline can reverse this steroid resistance in laboratory studies. Another commonly used drug, rosiglitazone can reverse smoking induced lung inflammation in laboratory studies. The investigators aim to study the effects of these drugs on smoking asthmatics' lung function and other parameters including quality of life and asthma control.

Detailed description

Smoking asthmatics have chronic pulmonary inflammation that is relatively steroid resistant. PPAR agonists (of which rosiglitazone is one example) have been shown to reduce several markers of inflammation in humans and in smoking animal models. This clinical study will use smoking asthmatics as a human model of smoke-induced steroid-insensitive airway inflammation to evaluate both efficacy of rosiglitazone as an anti-inflammatory drug as well as the effect of low doses of theophylline on the response to low-dose inhaled corticosteroid (LD ICS). Mild or moderate (as per GINA guidelines) persistent-asthmatic smokers will be randomised into this study after a 4-week washout period during which they will be withdrawn from inhaled corticosteroids (ICS). Subjects will then receive one of four treatments for 28 days: rosiglitazone, LD ICS, theophylline, or LD ICS plus theophylline. The effects of rosiglitazone and LD ICS on pulmonary function will be compared as a primary objective. In addition, effects of theophylline plus LD ICS will be compared against theophylline and LD ICS separately. Both pulmonary anti-inflammatory and systemic anti-inflammatory activity will also be investigated. Subjects will have baseline assessments of pulmonary function, biomarkers of systemic inflammation, sputum, exhaled breath biomarkers, asthma control questionnaires and safety parameters. Following 28 days of treatment, these parameters will all be reassessed in all subjects.

Conditions

• Asthma

Interventions

Type	Name	Description
DRUG	rosiglitazone	oral tablet, 4mg bd for 4 weeks
DRUG	theophylline	Oral theophylline, 200mg bd
DRUG	beclomethasone	inhaled beclomethasone, 200mcg bd
DRUG	inhaled beclomethasone and oral theophylline	inhaled beclomethasone (400mcg/day), oral theophylline (400mg/day)

Timeline

• Start date: 2005-07-01
• Completion: 2007-06-01
• First posted: 2005-07-13
• Last updated: 2010-01-27

Locations

1 site across 1 country: United Kingdom