PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe.
研究概览
简要总结
The overall purpose of this research is to gain understanding of the basic responses of the lung to inflammation. Inflammation is the way our bodies react to irritation or injury, and involves red, warm, and often painful swelling of the affected tissue. "Acute lung injury" involves a generalized inflammation to the lung that is activated by any of several conditions: infection, trauma, inhalation of toxic substances, etc. When lung injury is severe, not enough oxygen can get into the body; this can lead to the need for mechanical support of breathing (mechanical ventilation), problems with brain, heart or other organ function, and in some cases, death. Inducible nitric oxide synthase (iNOS) contributes to the development of lung inflammation.
详细描述
The investigators plan to use [18F](+/-)NOS (the F stands for fluorine and NOS stands for Nitric Oxide Synthase, the name for the investigational radioactive drug that targets iNOS) and positron emission tomography (PET) imaging as a measure of lung inflammation. PET is a machine that detects radiation and generates pictures using a donut shaped scanner similar in appearance to an x-ray "CAT" scan.
In order to show that [18F](+/-)NOS-PET is related to the amount of inflammation, the investigators first need to create a state of controlled lung inflammation that can be measured and quantified. "Controlled lung inflammation" means a reaction in the lungs that is similar to that which occurs during lung infection (increased respiratory secretions, and cough). It is "controlled" because the investigators will not be using anything alive or contagious (it will not spread from one part of your body to another, and cannot spread to another person) and a small area in only one lung will be affected. In order to create this state of controlled lung inflammation, the investigators plan to put a small amount of endotoxin into a single small section of the lung using a bronchoscope (a long, flexible, narrow tube that is passed through the nose or the mouth into the airways of the lung). This use of endotoxin is considered investigational. The investigators have received permission from the FDA to use endotoxin in this research study.
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
- 19 Years 至 44 Years(Adult)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy man or woman, any race or ethnicity, age 19 - 44 years old
- •Screening Pulmonary Function Test
- •Screening oxygen saturation by pulse oximetry >97% on room air
- •Capable of lying still and supine within the PET/CT scanner for 1.5 hours
- •Capable of following instructions for breathing protocol during CT portion of PET/CT
- •Able and willing to give informed consent
- •BMI < 35
排除标准
- •Pregnancy (confirmed by qualitative serum hCG pregnancy test)
- •Lactation
- •Active menstruation
- •History of cardiopulmonary disease
- •Currently taking any prescription medications
- •History of tobacco use or illicit drug use within the past year
- •Presence of implanted electronic medical device
- •Enrollment in another research study of an investigational drug
- •Known allergy to both trimethoprim/sulfamethoxazole and amoxicillin
- •Known allergy to drugs routinely used during bronchoscopy
- •Inability lie flat for 1.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT
研究组 & 干预措施
Endotoxin and [18F](+/-)NOS
All volunteers in this study will receive endotoxin in a single segment of the lung to induce mild, self-limited inflammation. They will also be imaged before and after endotoxin instillation with the novel PET tracer F-18 (+/-) NOS
干预措施: [18F](+/-)NOS (Drug)
结局指标
主要结局
Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe.
时间窗: Change in DVR on post-endotoxin scan (Day 2) from baseline (Day 1).
次要结局
- Bronchoalveolar lavage (BAL) fluid cell counts.(24 hours after endotoxin instillation.)
- Number and percent of iNOS-stained BAL cells.(24 hours after endotoxin instillation.)
研究者
Delphine L. Chen, MD
Assistant Professor of Radiology
Washington University School of Medicine
