Effect of Symbicort on GR Localisation in Asthma

NCT ID: NCT00159263

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30
• Study Completion Date: 2006-11-30

Brief 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.

Detailed 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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo

placebo

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Dry powder inhaler

Formoterol

Oxis(®) 12 μg

Group Type: EXPERIMENTAL

Formoterol Inhalant Powder

Intervention Type: DRUG

12ug

Budesonide low dose

Pulmicort(®) 200 μg

Group Type: EXPERIMENTAL

Budesonide Powder

Intervention Type: DRUG

Inhaler

Budesonide high dose

Pulmicort(®) 800 μg

Group Type: EXPERIMENTAL

Budesonide Powder

Intervention Type: DRUG

Inhaler

Budesonide/formoterol combination single

single 100/6 μg SYM100

Group Type: EXPERIMENTAL

Budesonide and Formoterol Product

Intervention Type: DRUG

Combination Inhaler, Symbicort

Budesonide/formoterol combination double

double 200/12 μg SYM200

Group Type: EXPERIMENTAL

Budesonide and Formoterol Product

Intervention Type: DRUG

Combination Inhaler, Symbicort

Interventions

Placebos

Dry powder inhaler

Intervention Type: DRUG

Formoterol Inhalant Powder

12ug

Intervention Type: DRUG

Budesonide Powder

Inhaler

Intervention Type: DRUG

Budesonide and Formoterol Product

Combination Inhaler, Symbicort

Intervention Type: DRUG

Other Intervention Names

Oxis; Pulmicort; Combination Inhaler, Symbicort

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergei A Kharitonov, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital

London, , United Kingdom

Countries

United Kingdom

References

Essilfie-Quaye S, Ito K, Ito M, Kharitonov SA, Barnes PJ. Comparison of Symbicort(R) versus Pulmicort(R) 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.

Reference Type: RESULT

PMID: 21903370 (View on PubMed)

Other Identifiers

BU-039-0005

Identifier Type: -

Identifier Source: org_study_id