AsthmaPhase 1NCT00327197
Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma
A Phase 1 study testing Prednisolone and Bronchoscopy in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
To evaluate and compare the expression and change in expression of key severe asthma targets at baseline in mile to moderate asthmatics vs. severe asthmatic subjects. To evaluate and compare the airway pathology at baseline and changes in airway pathology in relation to asthma severity. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- Prednisolone and Bronchoscopy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Aug 2005to 6 Jun 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of asthma with exclusion of other significant pulmonary disease.
- Body Mass Index between 19-31 kg.m-2.
- Subjects will be assigned to group 1(mild to moderate) or Group 2 (severe asthmatics) depending on their Lung Function test results.
Who cannot join
- As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study.
- History of drug or other allergy, which, in the opinion of the responsible physician, contra-indicates their participation.
- Subject is female who is pregnant or lactating.
- Currently or planning to take during the study regular medication (including over-the-counter) except for medication allowed in inclusion criteria.
- Having participated within 30 days or 5 half-lives, whichever is longer of the first dose in a study using new molecular entity, or the first dose in any other study investigating drugs or having participated within one month of the first dose in a study with invasive procedures.
- History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 2 weeks of baseline assessments.
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- History of abnormal bruising or bleeding.
- History of alcohol or drug abuse.
- Doing night-shift work within at least 5 days prior to dosing until completion of the study.
- Anticoagulants except low dose of Aspirin (80 mg per day) (for bronchoscopy).
- Beta blockers except for low dose Atenolol (25 mg/day) or Metoprolol (50 mg/day) (for bronchoscopy).
- Use of Cytochrome P450 inhibitors.
- History of hypersensitivity to any of the following medications: Lidocaine, Fentanyl, Versed, Demerol, Midazolam, Epinephrine, Flumazenil and Naloxone.
- History of hypersensitivity to bronchodilator (such as Albuterol).
- In addition, the following additional exclusion criteria must apply to mild to moderate persistent asthmatics on regular inhaled steroids:
- Changed asthma medication within the 4 weeks prior to screening.
- Has had an asthma exacerbation in the previous month.
- Known sensitivity or allergy to prednisolone.
- Current use or use within the previous 3 months of oral corticosteroids.
- Current use of Methotrexate, cyclosporine and PDE inhibitors
- History of tuberculosis, diabetes mellitus, osteoporosis, severe hypertension, glaucoma , severe affective disorder and peptic ulceration.
- In addition, the following additional exclusion criteria must apply to severe persistent asthmatics with clinical controlled asthma symptoms:
- Changed asthma medication within the 4 weeks prior to screening.
- Has had an asthma exacerbation in the previous month.
- sensitivity or allergy to prednisolone.
- History of tuberculosis, diabetes mellitus, osteoporosis, hypertension, glaucoma, severe affective disorder and peptic ulceration.
- Current use or use within the previous 4 weeks of oral prednisolone or equivalent of greater than 20mg daily.
- Current use of Methotrexate, cyclosporin.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Leicester, Leicestershire, LE3 9QP
About this study
Official title: A Study to Assess Disease Pathology and Key Therapeutic Targets in Severe Asthma
To evaluate and compare the expression and change in expression of key severe asthma targets at baseline in mile to moderate asthmatics vs. severe asthmatic subjects.
To evaluate and compare the airway pathology at baseline and changes in airway pathology in relation to asthma severity.
- Conditions
- Asthma
- Being tested
- Prednisolone, Bronchoscopy
- Keywords
- bronchoscopy, Sputum induction, Prednisolone, Asthma, biomarkers
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoloneDrug
Subjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days.
BronchoscopyProcedure or surgery
All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent mild steroid-naïve asthmatic group | Experimental | Asymptomatic subjects receiving only beta-agonist inhaler with predicted FEV1 >=80% and normal peak expiratory flow between attacks will be included. Receives: Drug: Prednisolone; Procedure: Bronchoscopy |
| Mild to moderate persistent asthmatic group | Experimental | Subjects with mild to moderate persistent asthma on low to moderate dose of inhaled corticosteroid (200-500 microgram fluticasone propionate daily or equivalent), an FEV1 >= 80% predicted (post-bronchodilator), and less than 20% variability in peak expiratory flow. Receives: Drug: Prednisolone; Procedure: Bronchoscopy |
| Severe asthma group | Experimental | Subjects with severe persistent asthma. They will be on either: high inhaled corticosteroid (CS >=1000 microgram fluticasone daily or equivalent) or on high dose inhaled CS plus oral CS (no more than 20 milligrams predisolone a day). The subjects should have at least one ( if on oral steroids) or two (if only on inhaled steroids) of the following: 1) FEV1<80% and FEV1/FVC ratio <70% 2) more than 25% variability in peak expiratory flow 3) daily symptoms ± nocturnal symptoms 4) severe exacerbations of >= twice a year in at least one of the last two years. Receives: Drug: Prednisolone; Procedure: Bronchoscopy |
| Healthy subjects group | Placebo comparator | Non-asthmatic and non-smokers with FEV1 > 85% predicted, on no regular medication. Receives: Procedure: Bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints
biomarkers, vital signs, ECG
Measured: Through 2 weeks of Prednisolone dosing
Secondary outcomes (1)
Expression of airway and systemic biomarkers. Relationship between changes in target expression and clinical measures of disease activity. Relationship between steady state plasma exposure of prednisolone and pharmacodynamic biomarkers.
biomarkers
Measured: Through 2 weeks of prednisolone dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2006 (estimated)
- Study start2 Aug 2005
- Primary completion6 Jun 2011
- Study completion6 Jun 2011
Why it stopped: The study was truncated due to the long period of enrollment and the collection of a sufficient amount of data that allowed the scientific objectives to be met
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 GlaxoSmithKlineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00327197
- Sponsor's protocol ID
- RES100769
- Status last verified
- Aug 2017
- First submitted
- 17 May 2006
- Last updated
- 4 Aug 2017
- Results posted
- No
Publications
Siddiqui S, Shikotra A, Richardson M, Doran E, Choy D, Bell A, Austin CD, Eastham-Anderson J, Hargadon B, Arron JR, Wardlaw A, Brightling CE, Heaney LG, Bradding P. Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis. J Allergy Clin Immunol. 2018 Nov;142(5):1457-1468. doi: 10.1016/j.jaci.2017.12.982. Epub 2018 Mar 14.
PubMed 29550052
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Assess Disease Pathology and Key Therapeutic Targets in Severe Asthma
- ClinicalTrials.gov ID
- NCT00327197
- Acronym / sponsor ID
- RES100769
- Conditions
- Asthma
- Keywords
- bronchoscopy, Sputum induction, Prednisolone, Asthma, biomarkers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was truncated due to the long period of enrollment and the collection of a sufficient amount of data that allowed the scientific objectives to be met
- Enrolment
- 47 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 2 Aug 2005 (actual)
- Primary completion
- 6 Jun 2011 (actual)
- Study completion
- 6 Jun 2011 (actual)
- First posted
- 18 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate and compare the expression and change in expression of key severe asthma targets at baseline in mile to moderate asthmatics vs. severe asthmatic subjects.
To evaluate and compare the airway pathology at baseline and changes in airway pathology in relation to asthma severity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Intermittent mild steroid-naïve asthmatic group | Experimental | Drug: Prednisolone, Procedure: BronchoscopyAsymptomatic subjects receiving only beta-agonist inhaler with predicted FEV1 >=80% and normal peak expiratory flow between attacks will be included. |
| Mild to moderate persistent asthmatic group | Experimental | Drug: Prednisolone, Procedure: BronchoscopySubjects with mild to moderate persistent asthma on low to moderate dose of inhaled corticosteroid (200-500 microgram fluticasone propionate daily or equivalent), an FEV1 >= 80% predicted (post-bronchodilator), and less than 20% variability in peak expiratory flow. |
| Severe asthma group | Experimental | Drug: Prednisolone, Procedure: BronchoscopySubjects with severe persistent asthma. They will be on either: high inhaled corticosteroid (CS >=1000 microgram fluticasone daily or equivalent) or on high dose inhaled CS plus oral CS (no more than 20 milligrams predisolone a day). The subjects should have at least one ( if on oral steroids) or two (if only on inhaled steroids) of the following: 1) FEV1<80% and FEV1/FVC ratio <70% 2) more than 25% variability in peak expiratory flow 3) daily symptoms ± nocturnal symptoms 4) severe exacerbations of >= twice a year in at least one of the last two years. |
| Healthy subjects group | Placebo comparator | Procedure: BronchoscopyNon-asthmatic and non-smokers with FEV1 > 85% predicted, on no regular medication. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- History of asthma with exclusion of other significant pulmonary disease.
- Body Mass Index between 19-31 kg.m-2.
- Subjects will be assigned to group 1(mild to moderate) or Group 2 (severe asthmatics) depending on their Lung Function test results.
Key exclusion criteria (28 listed)
- As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study.
- History of drug or other allergy, which, in the opinion of the responsible physician, contra-indicates their participation.
- Subject is female who is pregnant or lactating.
- Currently or planning to take during the study regular medication (including over-the-counter) except for medication allowed in inclusion criteria.
- Having participated within 30 days or 5 half-lives, whichever is longer of the first dose in a study using new molecular entity, or the first dose in any other study investigating drugs or having participated within one month of the first dose in a study with invasive procedures.
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 |
|---|---|---|
| PrednisoloneSubjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days. | Drug | Intermittent mild steroid-naïve asthmatic group, Mild to moderate persistent asthmatic group, Severe asthma group |
| BronchoscopyAll subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope. | Procedure or surgery | Healthy subjects group, Intermittent mild steroid-naïve asthmatic group, Mild to moderate persistent asthmatic group, Severe asthma group |
Primary outcome
Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints
Time frame: Through 2 weeks of Prednisolone dosing
biomarkers, vital signs, ECG
1 secondary outcome
Expression of airway and systemic biomarkers. Relationship between changes in target expression and clinical measures of disease activity. Relationship between steady state plasma exposure of prednisolone and pharmacodynamic biomarkers.
Time frame: Through 2 weeks of prednisolone dosing.
Results and safety
The study was stopped early (reason given: The study was truncated due to the long period of enrollment and the collection of a sufficient amount of data that allowed the scientific objectives to be met). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2017.
- Derived from this study: PubMed 29550052Siddiqui S, Shikotra A, Richardson M, Doran E, Choy D, Bell A, Austin CD, Eastham-Anderson J, Hargadon B, Arron JR, Wardlaw A, Brightling CE, Heaney LG, Bradding P. Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis. J Allergy Clin Immunol. 2018 Nov;142(5):1457-1468. doi: 10.1016/j.jaci.2017.12.982. Epub 2018 Mar 14.
- Results for study RES100769 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Prednisolone and Bronchoscopy in people with Asthma, run by GlaxoSmithKline 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 3 inclusion and 28 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: stopped early, as of the sponsor's last update on 4 Aug 2017. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was truncated due to the long period of enrollment and the collection of a sufficient amount of data that allowed the scientific objectives to be met). Results are not available in the source record.
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?
Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints (time frame: Through 2 weeks of Prednisolone dosing). 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 NCT00327197, 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 4 Aug 2017.