Development of Novel Non-invasive Inflammometry Following LPS Challenge in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Change in the number of total cells in bronchoalveolar lavage
研究概览
简要总结
The aim of this study is to further profile and develop the Lipopolysaccharide, endotoxin (LPS) challenge models (both by instillation and inhalation) by investigating the utility of various non-invasive monitoring methods.
详细描述
The hypothesis of the project is that local inflammatory changes in the lung induced by LPS can be captured by gas-enhanced Magnetic resonance imaging (MRI) and analysis of exhaled breath. While MRI is able to provide localized information on inflammatory processes, exhaled breath analysis can capture integral information over time. Assuming that these novel techniques correlate with cellular measures of inflammation, repetitive measurements to investigate onset and duration of action of investigational new drugs will be made possible.
The evaluation whether LPS induced changes in the lung can be captured and monitored by MRI will be performed by correlation of multiple endpoints describing the cellular composition of the airways with variables derived from MRI and breath analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female healthy subjects, aged 18-65 years. Women will be considered for inclusion if they are:
- •Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing. Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal, with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit).
- •Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence - the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to the first dose of study medication until at least 72 hours after treatment -, implants, injectables, combined oral contraceptives, hormonal IUDs or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).
- •Normal lung function with FEV1 predicted ≥ 80%
- •Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least the last five years
- •Able and willing to give written informed consent
排除标准
- •• Past or present disease, which as judged by the investigator, may affect the outcome of the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis)
- •Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, oral contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements
- •Clinically relevant history of allergy as judged by the investigator
- •Patient unable to undergo MRI (e.g. due to claustrophobia, cardiac pacemaker, hypersensitivity to MR i.v. contrast imaging agents)
- •Infections of the lower respiratory tract within 4 weeks before visit 1, visit 2, or visit
- •These patients can be rescreened starting from visit
- •Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs or ECG at Visit 1, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subject's ability to participate in the study
- •Elevated IgE
- •Intake of systemic or inhaled steroids in the previous 4 weeks before visit 1, visit 2, or visit 3
- •History of drug or alcohol abuse
- •Risk of non-compliance with study procedures
- •Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study
研究组 & 干预措施
LPS challenge
LPS inhalation and bronchial instillation
干预措施: LPS challenge (Procedure)
结局指标
主要结局
Change in the number of total cells in bronchoalveolar lavage
时间窗: change from baseline to 6 hours and 24 hours post LPS
次要结局
- The regional change in xenon uptake in dissolved-phase MRI(change from baseline to 6 hours and 24 hours post LPS)
- The regional change in oxygen transfer function assessed by MRI(change from baseline to 6 hours and 24 hours post LPS)
- The change of the number of exhaled particles(change from baseline to 6 hours and 24 hours post LPS)
研究者
Prof. Dr. Jens Hohlfeld
Division Director Airway Research
Fraunhofer-Institute of Toxicology and Experimental Medicine