A Bronchoscopy Study to Assess the Effects of Inhaled Corticosteroids on Adult Healthy Volunteers

NHS Trust

Status and phase

Active, not recruiting

Phase 4

Conditions

Healthy

Treatments

Device: Accuhaler

Drug: Fluticasone propionate

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02476825

168769

Details and patient eligibility

About

Full description

This is a randomized, single-blind, controlled, single centre bronchoscopy study designed to assess the effects of fluticasone propionate on airway gene expression and cellularity in healthy adult controls without asthma. This study will allow a more accurate assessment of the changes in gene/protein expression and cellularity that drive severe treatment-resistant asthma by allowing for the effects that are due to corticosteroids rather than the disease to be considered. This improved mechanistic understanding is important to identify novel therapeutic targets in severe asthma, and to support the development of novel therapeutics. The primary endpoint is the corticosteroid-inducible gene expression pattern in healthy airways.

Approximately 30 healthy adult subjects (age 18-65) will be randomised in a 2:1 ratio to one of two study groups: i) patients will receive fluticasone propionate 500 mcg b.i.d. via Accuhaler for 4 weeks (n=20), or ii) patients will receive no treatment for 4 weeks (n=10). Bronchoscopy will be performed in all patients at baseline, prior to the start of the treatment period and at the end of week 4. The PI, Genentech and Leicester laboratory support staff will be blinded to treatment allocation. A control arm is included to assess the repeatability of the planned analyses, the stability of the gene expression profiles measured during this study period, and to provide a comparator to the treatment group.

Written informed consent for participation in the study must be obtained before performing any study-specific tests or evaluations. Consent will be obtained at the screening visit. At screening, important co-morbidities will excluded . Patients will also be randomised at this screening visit.

To ensure there are sufficient data for analysis, if a subject withdraws before completion of the study, they will be replaced with another subject.

Enrollment

30 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Participant willing and able to give informed consent
Male or Female, aged 18-65 years at Visit 1
Forced expiratory volume at one second (FEV1) >80% predicted
FEV1/forced vital capacity (FVC) ratio ≥70%
Non-smoker for >1 year with <10 py smoking history
Female participants of child bearing potential must ensure use of effective contraception during the study
Participants has clinically acceptable laboratory and ECG at screening
A chest x-ray confirming the absence of significant lung disease
A negative result to skin prick testing with common aeroallergens, or, if a skin prick test to a common aeroallergen is positive, a negative response to challenge with methacholine (defined as a provocative concentration causing a 20% fall in FEV1 [PC20 methacholine] >16 mg/ml)
Able (in the Investigators opinion) and willing to comply with all study requirements

Exclusion criteria

Failure to meet the inclusion criteria
Female participants who are pregnant, lactating or planning pregnancy during the course of the study
History of a severe allergic reaction or anaphylaxis to corticosteroids
Systemic treatment with corticosteroids within last 6 months
Any infection that resulted in hospital admission for ≥ 24 hours within 4 weeks prior to Visit 1 or during screening
Any infection that required treatment with IV or intramuscular (IM) antibiotics within 4 weeks prior to Visit 1 or during screening
Any active infection that required treatment with oral antibiotics within 2 weeks prior to Visit 1 or during screening
Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening
Active tuberculosis requiring treatment within 12 months prior to Visit 1
Known immunodeficiency including but not limited to HIV infection
Evidence of acute or chronic hepatitis or known liver cirrhosis
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation ≥2.0 × the upper limit of normal (ULN) during screening
Clinically significant abnormality on screening ECG or laboratory tests (haematology, serum chemistry, and urinalysis) that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient or performing bronchoscopy
Known current malignancy or current evaluation for a potential malignancy
Unable to safely undergo elective flexible fiberoptic bronchoscopy because of any one of the following:
History of allergic reaction to local anesthetics to be used during the bronchoscopy
Presence of clinically significant abnormality on Screening Coagulation Panel
Presence of clinically significant medical comorbidities that, in the opinion of the investigator, may make the patient unsuitable for elective bronchoscopy or would impact on study efficacy assessments
A history of atopic disease (allergic rhinitis [perennial or seasonal], atopic dermatitis, food allergy)
History of alcohol or drug abuse that would impair or risk the patient's full participation in the study, in the opinion of the investigator
Current smoker, former smoker with smoking history of >10 pack-years.
Treatment with anticoagulant medications including but not limited to aspirin,warfarin or antiplatelet medication
Use of a licensed or investigational monoclonal antibody within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer)
Use of a systemic immunomodulatory or immunosuppressive therapy within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer).
Use of other investigational therapy not described above within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer)
Receipt of a live attenuated vaccine within 4 weeks prior to Visit 1
Use of complementary, alternative, or homeopathic medicines including, but not limited to traditional or non-traditional herbal medications within 3 months
Scheduled elective surgery or other procedures requiring general anaesthesia during the study
Donation of blood during the study or within the past 12 weeks
BMI >38 kg/m2
Body weight <40 kg