Rosiglitazone Versus Theophylline in Asthmatic Smokers

January 26, 2010 updated by: University of Glasgow

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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persistent-asthmatic smokers will be randomised into this study after a 4-week washout period during which they will be withdrawn from inhaled corticosteroids (ICS).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.

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Asthma Research Group, Gartnavel General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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 history
  • 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.

Exclusion Criteria:

  • 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 screening.
  • 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 therapy.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1
Inhaled beclomethasone (400mcg/day)
Drug: beclomethasone
inhaled beclomethasone, 200mcg bd
Other Names:
  • Qvar
Active Comparator: Arm 2
Rosiglitazone
Drug: rosiglitazone
oral tablet, 4mg bd for 4 weeks
Other Names:
  • Rosiglitazone Maleate, Avandia
Active Comparator: Arm3
Oral theophylline
Drug: theophylline
Oral theophylline, 200mg bd
Other Names:
  • 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 Names:
  • Qvar and uniphyllin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Comparison of pre-bronchodilator (FEV1) at 28 days between rosiglitazone and LD ICS treatment groups.
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Rosiglitazone vs LD ICS on other endpoints of pulmonary function in smoking asthmatics.
Time Frame: 28 days
28 days
Theophylline plus LD ICS vs LD ICS on pulmonary function in smoking asthmatics.
Time Frame: 28 days
28 days
Theophylline plus LD ICS vs theophylline on pulmonary function in smoking asthmatics.
Time Frame: 28 days
28 days
Safety and tolerability of rosiglitazone, LD ICS, theophylline and theophylline plus LD ICS in smoking asthmatics.
Time Frame: 28 days
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
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Glasgow

Collaborators

GlaxoSmithKline
Chief Scientist Office of the Scottish Government
Chest, Heart and Stroke Association Scotland

Investigators

  • Principal Investigator: Neil C Thomson, MD, University of Glasgow

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

July 1, 2005

First Submitted That Met QC Criteria

July 12, 2005

First Posted (Estimate)

July 13, 2005

Study Record Updates

Last Update Posted (Estimate)

January 27, 2010

Last Update Submitted That Met QC Criteria

January 26, 2010

Last Verified

November 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RES104033
  • 2004-004247-22 EUDRACT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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