Official Title: “Rationale for Therapy With Low Dose Steroids Combined With Long-Acting beta2-Agonists in Patients With Allergic Asthma: Redirecting Innate Immune Responses by Long-Term Treatment With High Doses of Inhaled Steroids”

This multi centre, double blind, comparator controlled, parallel group study is to determine whether asthma treatment with high doses of fluticasone propionate (FP) redirects a Th2/ eosinophil response towards a more treatment resistant neutrophil/ monocyte response and whether this occurs to a lesser extent in asthmatic subjects treated with the combination product of salmeterol and fluticasone propionate (SFC). The primary endpoint is the mean change in priming of blood neutrophils assessed by marker A17. After a run-in period of 4 weeks subjects will enter a 24 weeks high dose treatment (FP 500 mcg bd) or a 12 week medium-dose treatment with FP 250 mcg bd followed by a 12 week treatment with SFC 50/ 250 mcg. At the visits lung function measurements, ACT, eNO measurements and a blood sample will be performed. A total of 50 randomised subjects are planned to be recruited in this study

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: FLIXOTIDE and SERETIDE

Primary Measures

• Mean change in neutrophil priming in blood as assessed by marker A17

Secondary Measures

• - Activation in markers such as A27, CD11b, L-selection, CD16, CD32, VLA-4 and CD66b in whole blood - Cytokine/chemokine determination by multiplex assay in cell free serum - Asthma control measured - Lung function: FEV1, FVC and PEF - eNO

Inclusion:

• Positive skin prick test
• History of asthma (GINA)
• Regular treatment with FP with/without LABA at least 4 weeks before visit 1
• History of recurrent episodes of wheezing, breathlessness, chest tightness and/ or coughing in the previous year.
• Able to use a DISKUS™ inhaler
• Able perform reproducible lung function tests at Visit 1

Inclusion criteria treatment period:

• FEV1 % predicted > 70%
• ACT score < 25 after run-in period

Exclusion criteria run-in period:

• Hospitalised for asthma within 4 weeks prior to Visit 1
• Acute upper respiratory tract infection or a lower respiratory tract infection within 4 weeks prior to Visit 1
• Oral, parental or depot corticosteroids within 4 weeks prior to Visit 1
• Hepatic impairment or other significant disease

Exclusion criteria treatment period:

• Non-compliance (< 70%)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: GlaxoSmithKline

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, Prof. dr. Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00456313

Study ID Number: SAM109352

ClinicalTrials.gov Identifier: NCT00456313

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)