Rosiglitazone Versus Theophylline in Asthmatic Smokers
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.
|Asthma||Drug: rosiglitazone Drug: theophylline Drug: beclomethasone Drug: inhaled beclomethasone and oral theophylline||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Clinical Study to Investigate the Effect of Rosiglitazone, Theophylline and Inhaled Corticosteroid, Inflammation and Pulmonary Function in Asthmatic Smokers|
- Comparison of pre-bronchodilator (FEV1) at 28 days between rosiglitazone and LD ICS treatment groups. [ Time Frame: 28 days ]
- Rosiglitazone vs LD ICS on other endpoints of pulmonary function in smoking asthmatics. [ Time Frame: 28 days ]
- Theophylline plus LD ICS vs LD ICS on pulmonary function in smoking asthmatics. [ Time Frame: 28 days ]
- Theophylline plus LD ICS vs theophylline on pulmonary function in smoking asthmatics. [ Time Frame: 28 days ]
- Safety and tolerability of rosiglitazone, LD ICS, theophylline and theophylline plus LD ICS in smoking asthmatics. [ Time Frame: 28 days ]
- To assess the effects in smoking asthmatics of rosiglitazone, LD ICS, theophylline and theophylline plus LD ICS on asthma control using the ACQ (Juniper et al, 1999). [ Time Frame: 28 days ]
|Study Start Date:||July 2005|
|Study Completion Date:||June 2007|
Active Comparator: Group 1
Inhaled beclomethasone (400mcg/day)
inhaled beclomethasone, 200mcg bd
Other Name: Qvar
Active Comparator: Arm 2
oral tablet, 4mg bd for 4 weeks
Other Name: Rosiglitazone Maleate, Avandia
Active Comparator: Arm3
Oral theophylline, 200mg bd
Other Name: uniphyllin
Active Comparator: Arm 4
Oral theophylline and inhaled beclomethasone
Drug: inhaled beclomethasone and oral theophylline
inhaled beclomethasone (400mcg/day), oral theophylline (400mg/day)
Other Name: Qvar and uniphyllin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00119496
|Asthma Research Group, Gartnavel General Hospital|
|Glasgow, Scotland, United Kingdom, G12 0YN|
|Principal Investigator:||Neil C Thomson, MD||University of Glasgow|