AsthmaNCT00159263

Effect of Symbicort on GR Localisation in Asthma

A study testing Formoterol Inhalant Powder, Budesonide Powder and Budesonide and Formoterol Product in people with Asthma, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 21 to 60 years
Conditions the study is for: Asthma
What is being tested?: Formoterol Inhalant Powder, Budesonide Powder and Budesonide and Formoterol Product
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 10 participants
Where: 1 siteUnited Kingdom
Study dates: Nov 2004to Nov 2006
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Show all 10Show fewer

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 locations and contacts

1 site in 1 country.

United Kingdom1 site

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

Other trials in United Kingdom

About this study

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

Read the 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
Being tested: Placebos, Formoterol Inhalant Powder, Budesonide Powder, Budesonide and Formoterol Product
Keywords: Asthma, Glucocorticoid, Long-acting beta2-adrenoceptor, Inhaled corticosteroids
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlacebosDrug
Dry powder inhaler
Formoterol Inhalant PowderDrug
Also called Oxis
12ug
Budesonide PowderDrug
Also called Pulmicort
Inhaler
Budesonide and Formoterol ProductDrug
Also called Combination Inhaler, Symbicort
Combination Inhaler, Symbicort

Study groups in NCT00159263
Study group	Role	What they receive
Placebo	Placebo comparator	placebo Receives: Drug: Placebos
Formoterol	Experimental	Oxis(®) 12 μg Receives: Drug: Formoterol Inhalant Powder
Budesonide low dose	Experimental	Pulmicort(®) 200 μg Receives: Drug: Budesonide Powder
Budesonide high dose	Experimental	Pulmicort(®) 800 μg Receives: Drug: Budesonide Powder
Budesonide/formoterol combination single	Experimental	single 100/6 μg SYM100 Receives: Drug: Budesonide and Formoterol Product
Budesonide/formoterol combination double	Experimental	double 200/12 μg SYM200 Receives: Drug: Budesonide and Formoterol Product

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 1-2h
Changes in MKP-1 mRNA
Changes in MKP-1 mRNA measured by PCR
Measured: 1-2h
IL8 mRNA
Measured by PCR
Measured: 1-2h

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2004Nov 2006

First posted12 Sep 2005 (estimated)
Study startNov 2004
Primary completionNov 2006
Study completionNov 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by Imperial College LondonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00159263
Sponsor's protocol ID: BU-039-0005
Status last verified: Sep 2019
First submitted: 8 Sep 2005
Last updated: 27 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 21903370

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00159263
Acronym / sponsor ID: BU-039-0005
Conditions: Asthma
Keywords: Asthma, Glucocorticoid, Long-acting beta2-adrenoceptor, Inhaled corticosteroids
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Collaborators: AstraZeneca
Study start: Nov 2004 (actual)
Primary completion: Nov 2006 (actual)
Study completion: Nov 2006 (actual)
First posted: 12 Sep 2005 (estimated)
Results: Posted 27 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebosplacebo
Formoterol	Experimental	Drug: Formoterol Inhalant PowderOxis(®) 12 μg
Budesonide low dose	Experimental	Drug: Budesonide PowderPulmicort(®) 200 μg
Budesonide high dose	Experimental	Drug: Budesonide PowderPulmicort(®) 800 μg
Budesonide/formoterol combination single	Experimental	Drug: Budesonide and Formoterol Productsingle 100/6 μg SYM100
Budesonide/formoterol combination double	Experimental	Drug: Budesonide and Formoterol Productdouble 200/12 μg SYM200

Who may qualify

Ages: 21 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (10 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlacebosDry powder inhaler	Drug	Placebo
Formoterol Inhalant PowderAlso: Oxis12ug	Drug	Formoterol
Budesonide PowderAlso: PulmicortInhaler	Drug	Budesonide high dose, Budesonide low dose
Budesonide and Formoterol ProductAlso: Combination Inhaler, SymbicortCombination Inhaler, Symbicort	Drug	Budesonide/formoterol combination double, Budesonide/formoterol combination single

Primary outcome

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
Changes in MKP-1 mRNA
Time frame: 1-2h
Changes in MKP-1 mRNA measured by PCR
IL8 mRNA
Time frame: 1-2h
Measured by PCR

Results and safety

Results posted to the registry on 27 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	1	1
Formoterol	1	1
Budesonide Low Dose	2	2
Budesonide High Dose	2	2
Budesonide/Formoterol Single	2	2
Budesonide/Formoterol Double	2	2

Primary outcome: Changes in GR-GRE Binding

Time frame: 1-2h. Median (Inter-Quartile Range). Unit: GRE activity (OD)

Measure	Placebo n = 10	Formoterol n = 10	Budesonide Low Dose n = 10	Budesonide High Dose n = 10	Budesonide/Formoterol Combination Single n = 10	Budesonide/Formoterol Combination Double n = 10
Value	1.4 (0.5 to 2)	1.4 (0.3 to 2.6)	1.6 (0.7 to 2.0)	2.3 (1.1 to 7)	3.5 (1.3 to 6.1)	3 (1.5 to 6)

Placebo vs Budesonide/Formoterol Combination Single: p = 0.04, ANOVA

Population analysed: Crossover, each patient had all treatments

Primary outcome: Changes in MKP-1 mRNA

Time frame: 1-2h. Median (Inter-Quartile Range). Unit: MKP1/GNB2L1 ratio

Measure	Placebo n = 10	Formoterol n = 10	Budesonide Low Dose n = 10	Budesonide High Dose n = 10	Budesonide/Formoterol Combination Single n = 10	Budesonide/Formoterol Combination Double n = 10
Value	1 (0.1 to 1)	3 (1 to 44)	3 (2 to 70)	4 (4 to 51)	5 (3 to 150)	5 (3 to 150)

Placebo vs Budesonide/Formoterol Combination Double: p = 0.01, ANOVA

Primary outcome: IL8 mRNA

Time frame: 1-2h. Median (Inter-Quartile Range). Unit: IL8/GNB2L1 ratio

Measure	Placebo n = 10	Formoterol n = 10	Budesonide Low Dose n = 10	Budesonide High Dose n = 10	Budesonide/Formoterol Combination Single n = 10	Budesonide/Formoterol Combination Double n = 10
Value	1 (0.1 to 1.7)	4 (0.1 to 20)	4 (0.1 to 20)	0.4 (0.1 to 1.3)	0.2 (0.1 to 0.7)	0.2 (0.1 to 1.4)

Placebo vs Budesonide/Formoterol Combination Double: p = 0.04, ANOVA

Adverse events

Time frame: 1 year. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Formoterol	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Budesonide Low Dose	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Budesonide High Dose	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Budesonide/Formoterol Single	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Budesonide/Formoterol Double	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21903370Essilfie-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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sergei A Kharitonov, MD PhD principal investigator

Imperial College London

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Formoterol Inhalant Powder, Budesonide Powder and Budesonide and Formoterol Product in people with Asthma, run by Imperial College London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in GR-GRE Binding (time frame: 1-2h). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00159263, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2019.