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
  Purpose

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.


Condition Intervention Phase
Pneumonia
Drug: Endotoxin (E. coli O:113, Reference Endotoxin)
Drug: [18F](+/-)NOS
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 19
Study Start Date: December 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Endotoxin (E. coli O:113, Reference Endotoxin)
Other Name: Lipopolysaccharide
Drug: [18F](+/-)NOS

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.

  Eligibility

Ages Eligible for Study:   19 Years to 44 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407796

Locations
United States, Missouri
Washington University School of Medicne
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Barnes-Jewish Hospital
Investigators
Principal Investigator: Delphine L. Chen, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Delphine L. Chen, MD, Assistant Professor of Radiology, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01407796     History of Changes
Other Study ID Numbers: BJHF/ICTS 7326-01
Study First Received: July 28, 2011
Last Updated: April 17, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
lung inflammation
positron emission tomography (PET)
fluorodeoxyglucose (FDG)
inducible nitric oxide synthase (iNOS)
lung anti-inflammatory therapy

ClinicalTrials.gov processed this record on October 29, 2014