Nasal Lipopolysaccharide (LPS) Challenge in Healthy Volunteers (HVs): Investigation of Tolerability, Dose Response and the Expression Profile of Intercellular Adhesion Molecule-1 (ICAM-1)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis
研究概览
简要总结
The purpose of this study is to develop a nasal challenge model that causes a mild degree of inflammation, without causing any pain or symptoms, but that allows us to measure a variety of proteins in nasal secretions which causes inflammation in the nose. The nasal challenge model involves spraying the nostrils in the form of a fine mist with 4 different doses (1, 10, 30 and 100µg per nostril) of lipopolysaccharide (LPS) including a placebo. LPS is a type of protein which has been carefully purified from the outer cell wall of certain bacteria, is sterile and does not contain live bacteria, and will not cause infection.
The investigators will measure any inflammation in the nose by looking at cells collected by washing the inside of the nose (nasal lavage) and placing small strips of paper in the nasal cavity. The paper absorbs the nasal fluid and the chemicals produced during inflammation and can be extracted from the paper and analysed in the laboratory. The investigators will also be collecting a small amount of nasal epithelium taken by way of a nasal scrape; this is done by using a Rhinoprobe, a small plastic curette which is used to scrape a small piece of lining of the nose. The investigators hope that information obtained from this study will be used in future studies that will test new study drugs designed to treat diseases of the airways and lungs ( like asthma and chronic obstructive pulmonary disease (COPD) and hay fever.
详细描述
STUDY DESIGN AND METHODOLOGY This is a single-centre study which will be carried out at the Imperial Clinical Respiratory Research Unit (ICRRU) at St Mary's Hospital in London Paddington.
RECRUITMENT The study will recruit a total of 15 healthy participants.
STUDY VISITS The study will involve a total of 11 outpatients visits. The screening visit is the initial visit where the study is discussed with the participant and written informed consent is obtained by the PI or his designee. This is done prior to performing any study related procedures. The participant will have had the study information sheet for at least 24 hours prior to the visit.
The visit will include the collection of demographic data, height and weight, physical examination by a doctor, medical history, vital signs, body temperature, 12 lead ECG, laboratory assessments (safety bloods) urine drugs of abuse test and pregnancy tests for females. The participant will also be asked to indicate the presence of any nasal symptoms by completing a modified total nasal symptoms score sheet and perform a peak nasal inspiratory flow (PNIF) test.
If eligible, participants will be asked to return for further study visits. Participants will be given 4 different doses of LPS and a placebo in a randomised manner.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females aged 18 to 60 years
- •Current non-smokers for last 6 months (<5 cigs per week), with a smoking history of <5 pack years
- •BMI 20-30 kg/m2
排除标准
- •History of allergy
- •Upper airway infection in 2 weeks before screening
- •Lower respiratory tract infection in past 3 months
- •Treatment with local or systemic corticosteroids during previous 2 months
- •Signs or symptoms of chronic rhinitis, hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis
- •Previous nasal or sinus surgery
- •Clinically significant cardiovascular, hepatic, GIT, renal, endocrine, infective, haematological, neurological, dermatological, neoplastic conditions, gastro-oesophageal reflux, depression, TB
- •Participation in a therapeutic drug trial in the prior 30 days.
- •Medical therapy other than that permitted for contraception.
- •Positive pregnancy test
- •Inability or unwillingness to use contraception if the patient is a female of child-bearing age.
- •History of drug abuse or urine test showing evidence of recreational drug abuse
研究组 & 干预措施
Nasal LPS spray - placebo
This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS.
干预措施: Nasal LPS spray (Other)
Nasal LPS spray 1µg
This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS.
干预措施: Experimental: Nasal LPS spray 1µg (Other)
Nasal LPS spray 10 µg
This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS.
干预措施: Experimental: Nasal LPS spray 10 µg (Other)
Nasal LPS spray 30 µg
This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS.
干预措施: Experimental: Nasal LPS spray 30 µg (Other)
Nasal LPS spray 100 µg
This is a 5-way crossover, randomised, placebo-controlled study.
Arms consists of the following nasal challenges:
placebo, 1, 10, 30 and 100µg LPS.
干预措施: Experimental: Nasal LPS spray 100 µg (Other)
结局指标
主要结局
Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis
时间窗: 8 hours following nasal lipopolysaccharide (LPS) challenge
Measurement of gene expression (mRNA) for inter-cellular adhesion molecule-1 (ICAM-1) in nasal mucosal curettage samples, 8h following nasal lipopolysaccharide (LPS) challenge.
次要结局
- Nasal mucosal lining fluid IL-6 levels after nasal lipopolysaccharide (LPS) challenge(Up to 8h after nasal LPS challenge)
- Nasal mucosal lining fluid IL-1beta levels after nasal lipopolysaccharide (LPS) challenge(Up to 8h after nasal LPS challenge)
- Nasal mucosal lining fluid CXCL8 levels after nasal lipopolysaccharide (LPS)(Up to 8h after nasal LPS challenge)