PET Imaging of Endotoxin-induced iNOS Activation
Recruitment status was Recruiting
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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers|
- Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe. [ Time Frame: Change in DVR on post-endotoxin scan (Day 2) from baseline (Day 1). ] [ Designated as safety issue: No ]
- Bronchoalveolar lavage (BAL) fluid cell counts. [ Time Frame: 24 hours after endotoxin instillation. ] [ Designated as safety issue: No ]Total nucleated and neutrophil cell counts obtained by BAL after endotoxin instillation.
- Number and percent of iNOS-stained BAL cells. [ Time Frame: 24 hours after endotoxin instillation. ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Cells obtained by BAL will be stained for iNOS and 3-NT. The BAL fluid itself will be frozen and stored for later cytokine analysis.
White blood cells for iNOS and 3-NT staining and serum will be reserved for cytokine analyses.
Optional: DNA obtained from blood cells to measure the TLR4 polymorphisms.
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||November 2012|
|Estimated Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
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.
|Contact: Delphine Chen, MDfirstname.lastname@example.org|
|United States, Missouri|
|Washington University School of Medicne||Recruiting|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator: Delphine L. Chen, MD|
|Principal Investigator:||Delphine L. Chen, MD||Washington University School of Medicine|