Effect of Symbicort on GR Localisation in Asthma

Imperial College London

Status: Completed

Conditions: Asthma

Treatments: Drug: Placebos; Drug: Budesonide and Formoterol Product; Drug: Budesonide Powder; Drug: Formoterol Inhalant Powder

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00159263

BU-039-0005

Details and patient eligibility

About

To investigate a possible interaction between formoterol and budesonide on GR-translocation and to compare the effect of different doses of Symbicort (80/4.5 and 2x80/4.5 mcg) with the effect of budesonide (200 mcg and 800 mcg) on GR translocation, and to investigate the effect of the study drugs on exhaled NO (bronchial and alveolar fraction.

Full description

Combination therapy with inhaled corticosteroids (ICS) and long-acting β(2)-adrenergic agonists (LABA) is reported to have superior effects on controlling asthma symptoms to ICS alone; however, there is no molecular-based evidence to explain the clinical effects. Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophage.

In a randomised, double-blind cross-over placebo-controlled 6-visit study, 10 patients with mild asthma were given placebo, formoterol (Oxis(®) 12 μg), budesonide (Pulmicort(®) 200 μg :BUD200, or 800 μg :BUD800), or budesonide/formoterol combination (Symbicort(®)) as a single 100/6 μg (SYM100) or double 200/12 μg (SYM200) dose. Sputum macrophages were separated by plate adhesion from induced sputum. GR binding to the glucocorticoid-response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA. mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by quantitative RT-PCR.

Enrollment: 10 patients

Sex: All

Ages: 21 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with mild steroid-naïve asthma (ATS criteria) of either sex with FEV1 >70 % pred
• Able to produce sputum after sputum induction
• Exhaled NO (flow 50 ml/s) ≥ 20 ppb
• Written informed consent

Exclusion criteria

• Current upper respiratory tract infections
• Use of inhaled and/or oral GCS within 4 weeks prior to visit 1
• Treatment with antileukotrienes, theophylline, tiotropium and ipratropium within 2 weeks prior to screening visit
• Hypersensitivity to any of the investigational drugs or lactose
• Use of any beta blocking agent (including eye-drops)
• Women who are pregnant, breast-feeding or planning a pregnancy during the study. Women must be postmenopausal (at least one year must have passed after the last menstruation), surgically sterile or using acceptable contraceptives, as judged by the investigator
• Any significant disease or disorder (e.g. cardiovascular, pulmonary (other than asthma), gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subjects ability to participate in the study
• Inability to tolerate temporary withdrawal of bronchodilatory therapy
• Subjects not considered capable, as judged by the investigator, of following instructions of the study, e.g. because of a history of alcohol or drug abuse or any other reason
• Previous randomization in this study

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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10 participants in 6 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

placebo

Treatment:

Drug: Placebos

Formoterol

Experimental group

Description:

Oxis(®) 12 μg

Treatment:

Drug: Formoterol Inhalant Powder

Budesonide low dose

Experimental group

Description:

Pulmicort(®) 200 μg

Treatment:

Drug: Budesonide Powder

Budesonide high dose

Experimental group

Description:

Pulmicort(®) 800 μg

Treatment:

Drug: Budesonide Powder

Budesonide/formoterol combination single

Experimental group

Description:

single 100/6 μg SYM100

Treatment:

Drug: Budesonide and Formoterol Product

Budesonide/formoterol combination double

Experimental group

Description:

double 200/12 μg SYM200

Treatment:

Drug: Budesonide and Formoterol Product