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AsthmaPhase 1NCT00331058

Comparison Of Molecular Targets In Mild To Severe Asthmatics And Healthy Subjects

A Phase 1 study testing Bronchoscopsy and Prednisolone in people with Asthma, run by GlaxoSmithKline at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The primary goal of this study is to compare the expression of key GSK drug targets across the 4 asthma phenotypes and healthy subjects and secondarily to evaluate changes in target expression in response to a 2-week course of corticosteroids across the 4 asthma phenotypes. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Asthma
What is being tested?
Bronchoscopsy and Prednisolone
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
2 sitesUnited States
Study dates
18 Feb 2006to 7 Jul 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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Male or female subjects aged between 18-60 years inclusive at screening.
  • A female subject of childbearing potential must be using effective contraceptive
  • measures described in protocol for at least one month prior to Screening and should continue using the same contraceptive measure during the study until completion of follow-up procedures. Non child-bearing potential is defined as pre-menopausal females with documented (medical report verification) hysterectomy or surgical sterilisation, or post-menopausal women who have been amenorrheic for more than 1 year and having estradiol and FSH levels consistent with menopause.). Other methods include male partner who is sterile prior to female subject's entry into study and is the sole sexual partner for that female subject.
  • Atopic or non-atopic subjects
  • Able to comprehend the nature of this research protocol and other relevant medical information and the ability to give written informed consent prior to participation in the study.
  • Able to comply with the requirements and restrictions listed in the consent form.
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  • Available to complete the study and all measurements.
  • Read, comprehend, and write English at a sufficient level to complete study related materials.
  • Additional inclusion criteria for the steroid naïve intermittent asthmatics - Cohort A
  • Have a pre-history of a physician's diagnosis of asthma, with exclusion of other significant pulmonary
  • No significant disease other than asthma.
  • No history of steroid myopathy.
  • No history of recent exposure to live vaccine in the past 4 weeks and no intention to undergo live vaccination during the prednisolone trial or during the month following the trial.
  • Intermittent asthma with FEV1 ≥ 80% predicted.
  • Positive beta agonist reversibility as shown by greater than 12% improvement on FEV1or greater than 200ml improvement in FEV1 within 30 minutes following the administration of Albuterol Inhalation Aerosol OR a positive PC20 to Methacholine Challenge smaller than 16 mcg.
  • Not currently taking inhaled steroids (ICS), and has not taken ICS for at least 6 months prior to screening.
  • A non-smoker (as demonstrated by a negative urine cotinine) for at least the past 12 months with a pack history ≤5 pack years.
  • Additional inclusion criteria for the mild to moderate persistent asthmatics on regular inhaled steroids - Cohort B
  • Have a pre-history of a physician's diagnosis of asthma, with exclusion of other significant pulmonary diseases
  • No significant disease other than asthma.
  • No history of steroid myopathy.
  • No history of recent exposure to live vaccine in the past 4 weeks and no intention to undergo live vaccination during the prednisolone trial or during the month following the trial.
  • Mild to moderate persistent asthmatic with FEV1 ≥ 80% predicted
  • Asthma symptoms ranging from daily to less than once a day
  • Positive beta agonist reversibility as shown by greater than 12% improvement on FEV1or greater than 200ml improvement in FEV1 within 30 minutes following the administration of Albuterol Inhalation Aerosol OR a positive PC20 to Methacholine Challenge smaller than 16 mcg.
  • On regular inhaled steroid treatment (from 200-500 mcg FP daily or equivalent). Short and long acting beta-2 agonists, anti-cholinergies, and Leukotriene receptor antagonists are allowed as concurrent medication.
  • A non-smoker (as demonstrated by a negative urine cotinine) for at least the past 12 months with a pack history ≤5 pack years.
  • Additional inclusion criteria for the severe persistent asthmatics on maximal therapy; regular oral steroids - Cohort C
  • Have a pre-history of a physician's diagnosis of asthma, with exclusion of other significant pulmonary diseases
  • No significant disease other than asthma.
  • No history of steroid myopathy.
  • No history of recent exposure to live vaccine in the past 4 weeks and no intention to undergo live vaccination during the prednisolone trial or during the month following the trial.
  • Severe persistent asthmatic
  • Subjects should have at least one (if on oral steroids) or two (if only on inhaled steroids) of the following indices:
  • FEV1 <80% (post bronchodilator) and FEV1/FVC ratio <70% predicted;
  • Daily symptoms ± nocturnal symptoms as recorded in diary cards during run-in;
  • severe exacerbations (as defined FACET study Tattersfield 1999) of ≥ twice a year in at least one of the last two years, as recorded in clinical records
  • Positive beta agonist reversibility as shown by greater than 12% improvement on FEV1 or greater than 200ml improvement in FEV1 within 30 minutes following the administration of Albuterol Inhalation Aerosol OR a positive PC20 to Methacholine Challenge smaller than 16 mcg.
  • High dose inhaled steroids (≥ to 1000 mcg FP daily or equivalent), oral steroids of ≤ 20mg prednisolone a day or equivalent.
  • A non-smoker (as demonstrated by a negative urine cotinine) for at least the past 12 months with a pack history ≤5 pack years.
  • Additional inclusion criteria for the currently smoking, mild to moderate persistent asthmatics on maximal therapy; regular oral steroids - Cohort D
  • Have a pre-history of a physician's diagnosis of asthma, with exclusion of other significant pulmonary
  • No significant disease other than asthma.
  • No history of steroid myopathy.
  • No history of recent exposure to live vaccine in the past 4 weeks and no intention to undergo live vaccination during the prednisolone trial or during the month following the trial.
  • Smokers (as demonstrated by a positive urine cotinine) with a pack history >5 pack years
  • Mild to moderate persistent asthmatic with FEV1 ≥ 80% predicted
  • Asthma symptoms less than once a day
  • Positive beta agonist reversibility as shown by greater than 12% improvement on FEV1or greater than 200ml improvement in FEV1 within 30 minutes following the administration of Albuterol Inhalation Aerosol OR a positive PC20 to Methacholine Challenge smaller than 16mcg.
  • On regular inhaled steroid treatment (200-500 mcg FP daily or equivalent). (NB:
  • short and long acting beta-2 agonists, anti-cholinergies, and Leukotriene receptor antagonists are allowed as concurrent medication.) Additional inclusion criteria for healthy volunteers, non asthmatic, non smokers - Cohort E Healthy; defined as individuals who are free of significant cardiovascular, pulmonary (e.g. tuberculosis), gastrointestinal, hepatic, endocrine, renal, haematological, neurological and psychiatric disease as determined by medical history, physical examination and clinical chemistry/haematology/urinalysis investigation.
  • A non-smoker (as demonstrated by a negative urine cotinine) for at least the past 12 months with a pack history ≤5 pack years.

Who cannot join

  • As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study.
  • The subject has a 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.
  • Having participated within 30 days or 5 half-lives in a study receiving an investigational drug.
  • Having participated within 30 days in a study with an invasive procedure.
  • Donation of a 500 mL of blood within the previous 56 days or intention to donate within 56 days of the end of the last bronchoscopy.
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  • Evidence of recent infection that would preclude participation in the steroid trial in the judgement of the study physician. The subject may be deferred to later participation. History of abnormal bruising or bleeding.
  • History of alcohol or drug abuse within five years.
  • Positive urine test for drugs of abuse including alcohol at screen.
  • Abnormal (clinically significant) clinical laboratory test results.
  • Medical history of cirrhosis, hepatitis C or hepatitis B or HIV
  • Doing night-shift work that will change pattern within at least 5 days prior to study start through the first follow up visit for Cohorts A through D. This does not include the follow up visits at 6 and 12 months.
  • Female subjects who are unwilling or unable to use an appropriate method of contraception
  • Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
  • Concomitant medications that may interfere with study procedures or evaluations.
  • History of hypersensitivity to any of the following medications: Lidocaine, Fentanyl, Versed, Demerol, Midazolam, Epinephrine, Flumanzenil and Naloxon.
  • History of hypersensitivity to bronchodilator (such as Albuterol)
  • ALL WOMEN OF CHILD BEARING POTENTIAL WHO DO NOT WISH TO USE PROTOCOL APPROVED METHODS OF CONTRACEPTION WILL BE EXCLUDED.
  • Additional exclusion criteria for the steroid naïve intermittent asthmatics - Cohort A
  • Subject has changed asthma medication within 1 month prior to screening.
  • Subject had an asthma exacerbation in the previous month.
  • Known sensitivity or allergy to prednisolone.
  • History of tuberculosis, glaucoma, epilepsy, severe affective disorder or peptic ulceration.
  • Current use or use within the previous 1 month of oral corticosteroids.
  • Current use of any asthma medication except short acting inhaled β2 agonists
  • Current use of Methotrexate, cyclosporin, PDE inhibitors, azathioprine or other immunosuppressive agents, except steroids.
  • Additional exclusion criteria for the mild to moderate persistent asthmatics on regular inhaled steroids - Cohort B
  • Subject has changed asthma medication within 1 month prior to screening.
  • Subject had an asthma exacerbation in the previous month.
  • Known sensitivity or allergy to prednisolone.
  • History of tuberculosis, glaucoma, epilepsy, severe affective disorder or peptic ulceration.
  • Current use or use within the previous 1 month of oral corticosteroids.
  • Current use of Methotrexate, cyclosporin, PDE inhibitors, azathioprine or other immunosuppressive agents, except steroids.
  • Additional exclusion criteria for the severe persistent asthmatics on maximal therapy; regular oral steroids - Cohort C
  • Subject has changed asthma medication within 1 month prior to screening.
  • Subject had an asthma exacerbation in the previous month.
  • Known sensitivity or allergy to prednisolone.
  • History of tuberculosis, glaucoma, epilepsy, severe affective disorder or peptic ulceration.
  • Current use or use within the previous 1 month of oral prednisolone or equivalent of greater than 20mg daily.
  • Current use of Methotrexate, cyclosporin, PDE inhibitors, azathioprine or other immunosuppressive agents, except steroids.
  • Subjects should avoid any medications that in the opinion of the physician might interfere with either the safety of the subject or the interpretation of the results (e.g.
  • anti-inflammatory drugs)
  • Additional exclusion criteria for the currently smoking, mild to moderate persistent currently smoking asthmatics on regular inhaled steroids - Cohort D
  • Subject has changed asthma medication within 1 month prior to screening.
  • Subject had an asthma exacerbation in the previous month.
  • Known sensitivity or allergy to prednisolone.
  • History of tuberculosis, glaucoma, epilepsy, severe affective disorder or peptic ulceration.
  • Current use or use within the previous 1 month of oral corticosteroids.
  • Current use of Methotrexate, cyclosporin, PDE inhibitors, azathioprine or other immunosuppressive agents, except steroids.
  • Additional exclusion criteria for the healthy volunteers, non asthmatic non smokers - Cohort E The subject has any history of breathing problems in adult life (i.e. history of asthmatic symptoms). Screening lung function tests (FEV1) will be performed to confirm normal lung function parameters (≥80% predicted).

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19104

  • GSK Investigational Site

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: A Study To Validate Key Therapeutic Targets and Characterise Their Response to Corticosteroids in Multiple Asthma Phenotypes

The primary goal of this study is to compare the expression of key GSK drug targets across the 4 asthma phenotypes and healthy subjects and secondarily to evaluate changes in target expression in response to a 2-week course of corticosteroids across the 4 asthma phenotypes. Each asthmatic subject in this study will undergo two bronchoscopies. Each healthy subject will undergo one bronchoscopy.

Conditions
Asthma
Being tested
Bronchoscopsy, Prednisolone
Keywords
Severe Asthma bronchoscopy
Medical subject headings
Asthma

What participants receive

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

  • BronchoscopsyProcedure or surgery

    Healthy and Asthmatic Volunteers

  • PrednisoloneProcedure or surgery

    Asthmatic Volunteers

Study groups in NCT00331058
Study groupRoleWhat they receive
healthy volunteersOthercontrol group not receiving prednisolone
Receives: Procedure: Prednisolone
asthmatic volunteersOtherreceive prednisolone for 14-16 days
Receives: Procedure: Bronchoscopsy

What is being measured

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

  1. compare key drug targets across 4 asthma phenotypes and healthy subjects

    Measured: visits 3 through to and including visit 6

  2. evaluate changes in target expression in response to a 2 week course of corticosteroids across the 4 asthma phenotypes

    Measured: visits 3 through to and including visit 6

Secondary outcomes (16)
  1. Histopathology on bronchial biopsies

    Measured: visits 3 through to and including visit 6

  2. Cytospins

    Measured: visits 3 through to and including visit 6

  3. target protein expression

    Measured: visits 3 through to and including visit 6

  4. target expression in the blood

    Measured: visits 3 through to and including visit 6

  5. inflammatory markers

    Measured: visits 3 through to and including visit 6

  6. lung function

    Measured: visits 3 through to and including visit 6

  7. Radiological Parameters

    Measured: visits 3 through to and including visit 6

  8. Quality of life (QoL) and symptom scores

    Measured: visits 3 through to and including visit 6

  9. Changes in medication

    Measured: visits 3 through to and including visit 6

  10. Measures of pulmonary inflammation

    Measured: visits 3 through to and including visit 6

  11. Assessments of lung structure

    Measured: visits 3 through to and including visit 6

  12. activation state of a signalling pathway

    Measured: visits 3 through to and including visit 6

  13. Whole Blood TaqMan and/or transcriptomic analysis

    Measured: visits 3 through to and including visit 6

  14. new targets and biomarkers

    Measured: visits 3 through to and including visit 6

  15. TaqMan and/or Differential Gene Expression and Proteomics

    Measured: visits 3 through to and including visit 6

  16. Pharmacogenomics from blood samples

    Measured: visits 3 through to and including visit 6

Timeline

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

  1. First posted29 May 2006 (estimated)
  2. Study start18 Feb 2006
  3. Primary completion7 Jul 2011
  4. Study completion7 Jul 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

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
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00331058
Sponsor's protocol ID
RES100767
Status last verified
Jun 2017
First submitted
26 May 2006
Last updated
28 Jun 2017
Results posted
No
Data monitoring committee
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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bronchoscopsy and Prednisolone in people with Asthma, run by GlaxoSmithKline at 2 sites in United States.

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 52 inclusion and 50 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 28 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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. 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?

compare key drug targets across 4 asthma phenotypes and healthy subjects (time frame: visits 3 through to and including visit 6). The study lists 2 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 NCT00331058, 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 28 Jun 2017.

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