Effect of Symbicort on GR Localisation in Asthma

September 24, 2019 updated by: Imperial College London

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
placebo
Drug: Placebos
Dry powder inhaler
Experimental: Formoterol
Oxis(®) 12 μg
Drug: Formoterol Inhalant Powder
12ug
Other Names:
  • Oxis
Experimental: Budesonide low dose
Pulmicort(®) 200 μg
Drug: Budesonide Powder
Inhaler
Other Names:
  • Pulmicort
Experimental: Budesonide high dose
Pulmicort(®) 800 μg
Drug: Budesonide Powder
Inhaler
Other Names:
  • Pulmicort
Experimental: Budesonide/formoterol combination single
single 100/6 μg SYM100
Drug: Budesonide and Formoterol Product
Combination Inhaler, Symbicort
Other Names:
  • Combination Inhaler, Symbicort
Experimental: Budesonide/formoterol combination double
double 200/12 μg SYM200
Drug: Budesonide and Formoterol Product
Combination Inhaler, Symbicort
Other Names:
  • Combination Inhaler, Symbicort

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Sergei A Kharitonov, MD PhD, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2004

Primary Completion (Actual)

November 1, 2006

Study Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

September 27, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BU-039-0005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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