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Effect of Symbicort on GR Localisation in Asthma

Primary Purpose

Asthma

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Placebos
Formoterol Inhalant Powder
Budesonide Powder
Budesonide and Formoterol Product
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Asthma focused on measuring Asthma, Glucocorticoid, Long-acting beta2-adrenoceptor, Inhaled corticosteroids

Eligibility Criteria

21 Years - 60 Years (Adult)All SexesDoes not accept 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo

Formoterol

Budesonide low dose

Budesonide high dose

Budesonide/formoterol combination single

Budesonide/formoterol combination double

Arm Description

placebo

Oxis(®) 12 μg

Pulmicort(®) 200 μg

Pulmicort(®) 800 μg

single 100/6 μg SYM100

double 200/12 μg SYM200

Outcomes

Primary Outcome Measures

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
Changes in MKP-1 mRNA
Changes in MKP-1 mRNA measured by PCR
IL8 mRNA
Measured by PCR

Secondary Outcome Measures

Full Information

First Posted
September 8, 2005
Last Updated
September 24, 2019
Sponsor
Imperial College London
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00159263
Brief Title
Effect of Symbicort on GR Localisation in Asthma
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
November 2004 (Actual)
Primary Completion Date
November 2006 (Actual)
Study Completion Date
November 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma, Glucocorticoid, Long-acting beta2-adrenoceptor, Inhaled corticosteroids

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo
Arm Title
Formoterol
Arm Type
Experimental
Arm Description
Oxis(®) 12 μg
Arm Title
Budesonide low dose
Arm Type
Experimental
Arm Description
Pulmicort(®) 200 μg
Arm Title
Budesonide high dose
Arm Type
Experimental
Arm Description
Pulmicort(®) 800 μg
Arm Title
Budesonide/formoterol combination single
Arm Type
Experimental
Arm Description
single 100/6 μg SYM100
Arm Title
Budesonide/formoterol combination double
Arm Type
Experimental
Arm Description
double 200/12 μg SYM200
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Dry powder inhaler
Intervention Type
Drug
Intervention Name(s)
Formoterol Inhalant Powder
Other Intervention Name(s)
Oxis
Intervention Description
12ug
Intervention Type
Drug
Intervention Name(s)
Budesonide Powder
Other Intervention Name(s)
Pulmicort
Intervention Description
Inhaler
Intervention Type
Drug
Intervention Name(s)
Budesonide and Formoterol Product
Other Intervention Name(s)
Combination Inhaler, Symbicort
Intervention Description
Combination Inhaler, Symbicort
Primary Outcome Measure Information:
Title
Changes in GR-GRE Binding
Description
The GR-GRE binding is the glucocorticoid receptor (GR) DNA binding affinity. GR-GRE activity as assed by enzyme-immunosorbent assay
Time Frame
1-2h
Title
Changes in MKP-1 mRNA
Description
Changes in MKP-1 mRNA measured by PCR
Time Frame
1-2h
Title
IL8 mRNA
Description
Measured by PCR
Time Frame
1-2h

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sergei A Kharitonov, MD PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21903370
Citation
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.
Results Reference
result

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Effect of Symbicort on GR Localisation in Asthma

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