PET Imaging of Endotoxin-induced iNOS Activation

NCT ID: NCT01407796

Last Updated: 2014-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2012-04-30

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.

Conditions

Pneumonia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Endotoxin (E. coli O:113, Reference Endotoxin)

Intervention Type: DRUG

[18F](+/-)NOS

Intervention Type: DRUG

Interventions

Endotoxin (E. coli O:113, Reference Endotoxin)

Intervention Type: DRUG

[18F](+/-)NOS

Intervention Type: DRUG

Other Intervention Names

Lipopolysaccharide

Eligibility 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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Barnes-Jewish Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Delphine L. Chen, MD

Assistant Professor of Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Delphine L. Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicne

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 25525182 (View on PubMed)

Other Identifiers

BJHF/ICTS 7326-01

Identifier Type: -

Identifier Source: org_study_id