A Randomized, Open-labelled Bronchoscopy Study to Assess the Effects of Inhaled Corticosteroids (ICS) on Adult Healthy Volunteers
概览
- 阶段
- 4 期
- 干预措施
- Accuhaler
- 疾病 / 适应症
- Healthy
- 发起方
- University Hospitals, Leicester
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Relative change from baseline in airway tissue gene expression following 4-weeks of inhaled fluticasone propionate treatment
- 状态
- 进行中（未招募）
- 最后更新
- 2年前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Inhaled fluticasone
Inhaled fluticasone propionate (via dry powder inhaler \[Accuhaler\]), 500 micrograms b.i.d. for 4 weeks
干预措施: Accuhaler
Inhaled fluticasone
Inhaled fluticasone propionate (via dry powder inhaler \[Accuhaler\]), 500 micrograms b.i.d. for 4 weeks
干预措施: Fluticasone propionate
结局指标
主要结局
Relative change from baseline in airway tissue gene expression following 4-weeks of inhaled fluticasone propionate treatment
时间窗: 6 months after last patient visit
次要结局
- Relative change from baseline in airway cellularity following 4-weeks of inhaled fluticasone propionate treatment(18 months after last patient visit)
- Relative change from baseline in peripheral blood gene expression following 4-weeks of inhaled fluticasone propionate treatment(18 months after last patient visit)
- Differentiate pathways, biomarkers, and heterogeneity between gene expression and pathophysiology in severe asthmatics on ICS +/- lebrikizumab (separate Genentech-sponsored study known as CLAVIER) and healthy volunteers on ICS(18 months after last patient visit)
- Relative change from baseline in airway protein expression following 4-weeks of inhaled fluticasone propionate treatment(18 months after last patient visit)