Rosiglitazone Versus Theophylline in Asthmatic Smokers

NCT00119496 | Completed Phase 2

• 2 other identifiers: RES1040332004-004247-22 EUDRACT
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Asthma

Keywords

Corticosteroid; Rosiglitazone; Theophylline; Beclomethasone; Inflammation; Asthma; Smoking; Pulmonary

Outcome Measures

Primary Outcomes (1)

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

  28 days

Secondary Outcomes (5)

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

  28 days

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

  28 days

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

  28 days

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

  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).

  28 days

Study Arms (4)

Group 1

ACTIVE COMPARATOR

Inhaled beclomethasone (400mcg/day)

Drug: beclomethasone

Arm 2

ACTIVE COMPARATOR

Rosiglitazone

Drug: rosiglitazone

Arm3

ACTIVE COMPARATOR

Oral theophylline

Drug: theophylline

Arm 4

ACTIVE COMPARATOR

Oral theophylline and inhaled beclomethasone

Drug: inhaled beclomethasone and oral theophylline

Interventions

rosiglitazone DRUG

oral tablet, 4mg bd for 4 weeks

Also known as: Rosiglitazone Maleate, Avandia

Arm 2

theophylline DRUG

Oral theophylline, 200mg bd

Also known as: uniphyllin

Arm3

beclomethasone DRUG

inhaled beclomethasone, 200mcg bd

Also known as: Qvar

Group 1

inhaled beclomethasone and oral theophylline DRUG

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

Also known as: Qvar and uniphyllin

Arm 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Glasgow: lead
• GlaxoSmithKline: collaborator
• Chest, Heart and Stroke Association Scotland: collaborator
• Chief Scientist Office of the Scottish Government: collaborator

Study Sites (1)

Asthma Research Group, Gartnavel General Hospital

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 17177672 BACKGROUND

• 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.

  PMID: 19196814 DERIVED

Related Links

• Asthma Research Unit website

MeSH Terms

Conditions

Asthma; Inflammation; Smoking

Interventions

Rosiglitazone; Theophylline; Beclomethasone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated

Study Officials

• Neil C Thomson, MD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 1, 2005
• First Posted: July 13, 2005
• Study Start: July 1, 2005
• Study Completion: June 1, 2007
• Last Updated: January 27, 2010

Record last verified: 2007-11

Locations

GB (1)