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AsthmaPhase 2/3NCT00119496

Rosiglitazone Versus Theophylline in Asthmatic Smokers

A Phase 2/3 study testing rosiglitazone, theophylline and beclomethasone in people with Asthma, run by University of Glasgow at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Asthma
What is being tested?
rosiglitazone, theophylline and beclomethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
1 siteUnited Kingdom
Study dates
Jul 2005to Jun 2007
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 24Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Asthma Research Group, Gartnavel General Hospital

    Glasgow, Scotland, G12 0YN

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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
Being tested
rosiglitazone, theophylline, beclomethasone, inhaled beclomethasone and oral theophylline
Keywords
Corticosteroid, Rosiglitazone, Theophylline, Beclomethasone, Inflammation, Asthma, Smoking, Pulmonary
Medical subject headings
Asthma, Inflammation, Smoking

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rosiglitazoneDrug

    Also called Rosiglitazone Maleate, Avandia

    oral tablet, 4mg bd for 4 weeks

  • theophyllineDrug

    Also called uniphyllin

    Oral theophylline, 200mg bd

  • beclomethasoneDrug

    Also called Qvar

    inhaled beclomethasone, 200mcg bd

  • inhaled beclomethasone and oral theophyllineDrug

    Also called Qvar and uniphyllin

    inhaled beclomethasone (400mcg/day), oral theophylline (400mg/day)

Study groups in NCT00119496
Study groupRoleWhat they receive
Group 1Active comparatorInhaled beclomethasone (400mcg/day)
Receives: Drug: beclomethasone
Arm 2Active comparatorRosiglitazone
Receives: Drug: rosiglitazone
Arm3Active comparatorOral theophylline
Receives: Drug: theophylline
Arm 4Active comparatorOral theophylline and inhaled beclomethasone
Receives: Drug: inhaled beclomethasone and oral theophylline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Comparison of pre-bronchodilator (FEV1) at 28 days between rosiglitazone and LD ICS treatment groups.

    Measured: 28 days

Secondary outcomes (5)

  1. Rosiglitazone vs LD ICS on other endpoints of pulmonary function in smoking asthmatics.

    Measured: 28 days

  2. Theophylline plus LD ICS vs LD ICS on pulmonary function in smoking asthmatics.

    Measured: 28 days

  3. Theophylline plus LD ICS vs theophylline on pulmonary function in smoking asthmatics.

    Measured: 28 days

  4. Safety and tolerability of rosiglitazone, LD ICS, theophylline and theophylline plus LD ICS in smoking asthmatics.

    Measured: 28 days

  5. 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).

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2005 (estimated)
  2. Study startJul 2005
  3. Study completionJun 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00119496
Sponsor's protocol ID
RES104033
Other IDs
2004-004247-22 EUDRACT, 2004
Status last verified
Nov 2007
First submitted
1 Jul 2005
Last updated
27 Jan 2010
Results posted
No
Data monitoring committee
No

Publications

  • 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. doi: 10.1111/j.1365-2222.2006.02604.x.

    PubMed 17177672

  • Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, Lafferty J, Chaudhuri R, Braganza G, Adcock IM, Barnes PJ, Wood S, Thomson NC. Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study. Eur Respir J. 2009 May;33(5):1010-7. doi: 10.1183/09031936.00158208. Epub 2009 Feb 5.

    PubMed 19196814

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing rosiglitazone, theophylline and beclomethasone in people with Asthma, run by University of Glasgow at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of pre-bronchodilator (FEV1) at 28 days between rosiglitazone and LD ICS treatment groups. (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00119496, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2010.

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