Rosiglitazone Versus Theophylline in Asthmatic Smokers
Information source: University of Glasgow
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: rosiglitazone (Drug); theophylline (Drug); beclomethasone (Drug); inhaled beclomethasone and oral theophylline (Drug)
Phase: Phase 2/Phase 3
Sponsored by: University of Glasgow
Official(s) and/or principal investigator(s):
Neil C Thomson, MD, Principal Investigator, Affiliation: University of Glasgow
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
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
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.
Official title: A Clinical Study to Investigate the Effect of Rosiglitazone, Theophylline and Inhaled Corticosteroid, Inflammation and Pulmonary Function in Asthmatic Smokers
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Comparison of pre-bronchodilator (FEV1) at 28 days between rosiglitazone and LD ICS treatment groups.
Rosiglitazone vs LD ICS on other endpoints of pulmonary function in smoking asthmatics.
Theophylline plus LD ICS vs LD ICS on pulmonary function in smoking asthmatics.
Theophylline plus LD ICS vs theophylline on pulmonary function in smoking asthmatics.
Safety and tolerability of rosiglitazone, LD ICS, theophylline and theophylline plus LD ICS in smoking asthmatics.
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).
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
Minimum age: 18 Years.
Maximum age: 60 Years.
- Males or females between 18 and 60 years of age (inclusive).
- Clinical diagnosis of mild or moderate persistent asthma in accordance with the
Global Initiative for Asthma (GINA) criteria
- Have had a history of asthma for a minimum of 6 months prior to entry into the study
- Subjects must be current cigarette smokers with a minimum five-pack-year smoking
- Baseline FEV1 that is greater than 50% predicted; and reversibility of 12% or more at
screening, washout or randomisation.
- Capable of providing signed written informed consent and complying with all the
specified study procedures.
- Asthma exacerbation or a respiratory tract infection within four weeks of screening.
- Type 1 or type 2 diabetes mellitus.
- Women who are lactating, pregnant, or planning to become pregnant.
- Clinically significant renal or hepatic laboratory values (e. g. AST/ALT/total
bilirubin/AP > 2. 5 times normal values).
- Anaemia (< 11 g/dL for males or < 10 g/dL for females)
- Contraindications to treatment as outlined in any of the product labels
- Prior history of severe oedema or serious fluid related event (e. g., heart failure)
associated with any TZD
- The subject has a history of significant hypersensitivity to study drugs
- Presence of unstable or severe angina or congestive heart failure (NYHA class III/IV)
or evidence or history of known congestive heart failure (NYHA class I-IV) or an
abnormal electrocardiogram (ECG), as determined by the Investigator, or subjects who
have had new cardiac events (such as MI, new CHF, PTCA, CABG) within 6 months of
- History or suspicion of current drug abuse or alcohol abuse within the last 6 months.
- History suggestive of active infection or non-asthma lung pathology
- Clinically significant renal disease, metabolic syndrome, cirrhosis (Child-Pugh Class
B/C), hypertension or any other clinically significant cardiovascular, neurological,
endocrine, or haematological abnormalities that are uncontrolled on permitted
- Risk factors for human immunodeficiency virus (HIV), hepatitis B or hepatitis C
infection at Screening (Visit 1)
- Subjects who are morbidly obese, defined as having a body mass index (BMI) > 40 kg/m2
- Unable to perform spirometry
- Subjects who require treatment with any of the following asthma medications from
Screening (Visit 1) until study completion:
- Inhaled cromolyn sodium or nedocromil;
- Ipratropium bromide;
- Xanthines (theophylline preparations);
- Leukotriene modifiers;
- Long-acting inhaled beta2-agonists (salmeterol, formoterol);
- Oral beta2-agonists.
- Treatment with oral, intravenous or intra-articular corticosteroids within 6 weeks of
Screening or thereafter.
- Subjects who have been taking in excess of 1000 μg daily of beclomethasone (or
equivalent) within 6 weeks of Screening
Locations and Contacts
Asthma Research Group, Gartnavel General Hospital, Glasgow, Scotland G12 0YN, United Kingdom
Asthma Research Unit website
Spears M, McSharry C, Thomson NC. Peroxisome proliferator-activated receptor-gamma agonists as potential anti-inflammatory agents in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 2006 Dec;36(12):1494-504. Review.
Starting date: July 2005
Last updated: January 26, 2010