Effect of Symbicort on GR Localisation in Asthma

Asthma Clinical Trial

Official title:

Effect of Symbicort on GR (Glucocorticoid Receptor) Translocation in Induced Sputum in Comparison With Budesonide, Formoterol and Placebo. A Single Dose Exploratory Study in Patients With Mild Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00159263
• Other study ID #: BU-039-0005
• Status: Completed
• Phase: N/A
• Start date: November 2004
• Est. completion date: November 2006

Study information

• Verified date: September 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2006
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Placebos
Dry powder inhaler
• Formoterol Inhalant Powder
12ug
• Budesonide Powder
Inhaler
• Budesonide and Formoterol Product
Combination Inhaler, Symbicort

Locations

Country	Name	City	State
United Kingdom	Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Essilfie-Quaye S, Ito K, Ito M, Kharitonov SA, Barnes PJ. Comparison of Symbicort® versus Pulmicort® on steroid pharmacodynamic markers in asthma patients. Respir Med. 2011 Dec;105(12):1784-9. doi: 10.1016/j.rmed.2011.08.020. Epub 2011 Sep 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in GR-GRE Binding	The GR-GRE binding is the glucocorticoid receptor (GR) DNA binding affinity. GR-GRE activity as assed by enzyme-immunosorbent assay	1-2h
Primary	Changes in MKP-1 mRNA	Changes in MKP-1 mRNA measured by PCR	1-2h
Primary	IL8 mRNA	Measured by PCR	1-2h