No Resistance After Long Term Treatment SERETIDE

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: FLIXOTIDE and SERETIDE


Participation Criteria
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Eligibility Criteria
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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%)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: arm 1<br> | Drug: FLIXOTIDE and SERETIDE<br>* comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in neutrophil priming in blood as assessed by marker A17 |  | on going | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | on going | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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innate immune response, asthma, fluticasone propionate, salmeterol/fluticasone propionate, combination product, neutrophil priming