PET Imaging of Endotoxin-induced iNOS Activation

Tracking Information
First Submitted Date ICMJE	July 28, 2011
First Posted Date ICMJE	August 2, 2011
Last Update Posted Date	April 21, 2014
Study Start Date ICMJE	December 2010
Actual Primary Completion Date	April 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 29, 2011)	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). ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01407796 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 29, 2011)	Bronchoalveolar lavage (BAL) fluid cell counts. [ Time Frame: 24 hours after endotoxin instillation. ]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. ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	PET Imaging of Endotoxin-induced iNOS Activation
Official Title ICMJE	PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers
Brief Summary	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.
Detailed Description	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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
Condition ICMJE	Pneumonia
Intervention ICMJE	Drug: Endotoxin (E. coli O:113, Reference Endotoxin) Other Name: Lipopolysaccharide; Drug: [18F](+/-)NOS
Study Arms	Experimental: 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; Interventions: Drug: Endotoxin (E. coli O:113, Reference Endotoxin); Drug: [18F](+/-)NOS
Publications *	Huang HJ, Isakow W, Byers DE, Engle JT, Griffin EA, Kemp D, Brody SL, Gropler RJ, Miller JP, Chu W, Zhou D, Pierce RA, Castro M, Mach RH, Chen DL. Imaging pulmonary inducible nitric oxide synthase expression with PET. J Nucl Med. 2015 Jan;56(1):76-81. doi: 10.2967/jnumed.114.146381. Epub 2014 Dec 18.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 17, 2014)	19
Original Estimated Enrollment ICMJE; (submitted: July 29, 2011)	11
Actual Study Completion Date	April 2012
Actual Primary Completion Date	April 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 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 Exclusion Criteria: 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
Sex/Gender	Sexes Eligible for Study: All
Ages	19 Years to 44 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01407796
Other Study ID Numbers ICMJE	BJHF/ICTS 7326-01
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Delphine L. Chen, MD, Washington University School of Medicine
Study Sponsor ICMJE	Washington University School of Medicine
Collaborators ICMJE	Barnes-Jewish Hospital
Investigators ICMJE	Principal Investigator: Delphine L. Chen, MD Washington University School of Medicine
PRS Account	Washington University School of Medicine
Verification Date	April 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP