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| Sponsor: | University of Glasgow |
|---|---|
| Collaborators: |
GlaxoSmithKline Chest, Heart and Stroke Association Scotland Chief Scientist Office of the Scottish Government |
| Information provided by: | University of Glasgow |
| ClinicalTrials.gov Identifier: | NCT00119496 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Asthma |
Drug: rosiglitazone Drug: theophylline Drug: beclomethasone Drug: inhaled beclomethasone and oral theophylline |
Phase II Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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 |
| Enrollment: | 79 |
| Study Start Date: | July 2005 |
| Study Completion Date: | June 2007 |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Group 1
Inhaled beclomethasone (400mcg/day)
|
Drug: beclomethasone
inhaled beclomethasone, 200mcg bd
Other Name: Qvar
|
|
Active Comparator: Arm 2
Rosiglitazone
|
Drug: rosiglitazone
oral tablet, 4mg bd for 4 weeks
Other Name: Rosiglitazone Maleate, Avandia
|
|
Active Comparator: Arm3
Oral theophylline
|
Drug: theophylline
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.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Subjects who require treatment with any of the following asthma medications from Screening (Visit 1) until study completion:
Contacts and Locations| United Kingdom | |
| Asthma Research Group, Gartnavel General Hospital | |
| Glasgow, Scotland, United Kingdom, G12 0YN | |
| Principal Investigator: | Neil C Thomson, MD | University of Glasgow |
More Information
| ClinicalTrials.gov Identifier: | NCT00119496 History of Changes |
| Other Study ID Numbers: | RES104033, 2004-004247-22 EUDRACT |
| Study First Received: | July 1, 2005 |
| Last Updated: | January 26, 2010 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
|
Corticosteroid Rosiglitazone Theophylline Beclomethasone |
Inflammation Asthma Smoking Pulmonary |
|
Asthma Inflammation Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Pathologic Processes Beclomethasone Theophylline Rosiglitazone Anti-Inflammatory Agents |
Therapeutic Uses Pharmacologic Actions Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Bronchodilator Agents Autonomic Agents |