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

NCT00331058 | Terminated Phase 1

• 1 other identifier: RES100767
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief 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. Each asthmatic subject in this study will undergo two bronchoscopies. Each healthy subject will undergo one bronchoscopy.

Conditions

Asthma

Keywords

Severe Asthma bronchoscopy

Outcome Measures

Primary Outcomes (2)

• compare key drug targets across 4 asthma phenotypes and healthy subjects

  visits 3 through to and including visit 6

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

  visits 3 through to and including visit 6

Secondary Outcomes (16)

• Histopathology on bronchial biopsies

  visits 3 through to and including visit 6

• Cytospins

  visits 3 through to and including visit 6

• target protein expression

  visits 3 through to and including visit 6

• target expression in the blood

  visits 3 through to and including visit 6

• inflammatory markers

  visits 3 through to and including visit 6

Study Arms (2)

healthy volunteers

OTHER

control group not receiving prednisolone

Procedure: Prednisolone

asthmatic volunteers

OTHER

receive prednisolone for 14-16 days

Procedure: Bronchoscopsy

Interventions

Bronchoscopsy PROCEDURE

Healthy and Asthmatic Volunteers

asthmatic volunteers

Prednisolone PROCEDURE

Asthmatic Volunteers

healthy volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Available to complete the study and all measurements.
• Read, comprehend, and write English at a sufficient level to complete study related materials.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 29550052 DERIVED

Related Links

• Results for study RES100767 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Asthma

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: February 18, 2006
• Primary Completion: July 7, 2011
• Study Completion: July 7, 2011
• Last Updated: June 28, 2017

Record last verified: 2017-06

Locations

US (2)