PET Imaging of Endotoxin-induced iNOS Activation

This study has been completed.
Sponsor:
Collaborator:
Barnes-Jewish Hospital
Information provided by (Responsible Party):
Delphine L. Chen, MD, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01407796
First received: July 28, 2011
Last updated: April 17, 2014
Last verified: April 2014

July 28, 2011
April 17, 2014
December 2010
April 2012   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01407796 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
PET Imaging of Endotoxin-induced iNOS Activation
PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers

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.

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.

Interventional
Phase 1
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Pneumonia
  • Drug: Endotoxin (E. coli O:113, Reference Endotoxin)
    Other Name: Lipopolysaccharide
  • Drug: [18F](+/-)NOS
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
April 2012
April 2012   (final data collection date for primary outcome measure)

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
Both
19 Years to 44 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01407796
BJHF/ICTS 7326-01
Yes
Delphine L. Chen, MD, Washington University School of Medicine
Washington University School of Medicine
Barnes-Jewish Hospital
Principal Investigator: Delphine L. Chen, MD Washington University School of Medicine
Washington University School of Medicine
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP