PET Imaging of Endotoxin-induced iNOS Activation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Washington University School of Medicine.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Barnes-Jewish Hospital
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01407796
First received: July 28, 2011
Last updated: July 29, 2011
Last verified: July 2011
  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 Phase
Pneumonia
Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers

Resource links provided by NLM:


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 ]

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.


Estimated Enrollment: 11
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)
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
Sampling Method:   Probability Sample
Study Population

Healthy man or woman, any race or ethnicity, age 19 - 44 years old.

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

Contacts
Contact: Delphine Chen, MD 314-362-7029 chend@mir.wustl.edu

Locations
United States, Missouri
Washington University School of Medicne Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Delphine L. Chen, MD         
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: Dr. 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: July 29, 2011
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

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on April 17, 2014