Assessing NOS Uptake With PET Imaging in Lung Inflammation

NCT02151552 | Completed Early Phase 1 DMC

• 1 other identifier: DDCF 2010060-201403017
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn more about the basic responses of the lungs to inflammation using positron emission tomography, or PET, imaging scans of the lungs. PET is a machine that detects radiation and generates pictures using a donut-shaped scanner similar in appearance to an x-ray "CAT" or computed tomography (CT) scan or an MRI. Inflammation is the way our bodies react to irritation or injury, and involves red, warm, and often painful swelling of the affected tissue. An enzyme called inducible nitric oxide synthase (iNOS) contributes to the development of lung inflammation.

Conditions

Lung Inflammation

Keywords

lung inflammation; positron emission tomography; inducible nitric oxide synthase

Outcome Measures

Primary Outcomes (1)

• Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe

  Comparison of DVR by Logan plot for \[18F\](+/-)NOS uptake, pulmonary blood flow (PBF) and extravascular lung water (EVLW) in the regions of interest generated from scans obtained before and after endotoxin instillation and in the right and left lungs will be compared using a repeated-measures t-test, with statistical significance set at p\<0.05. The DVR determined for \[18F\](+/-)NOS normalized for either PBF or EVLW will also be compared using a repeated-measures t-test before and after endotoxin as well as in the right and left lungs to determine whether differences in \[18F\](+/-)NOS uptake depend on either PBF or EVLW.

  Change in DVR on post-endotoxin PET scan (Day 2) from baseline (Day 1)

Secondary Outcomes (9)

• Change in DVR in right middle lobe

  post-endotoxin scan (Day 2) from baseline (Day 1) scan

• Mean Hounsfield units (HU), measure of density on CT images, in right middle lobe and lingula

  baseline PET/CT scan on Day 1 to post-endotoxin scan on Day 2

• Change in HU in right middle lobe and lingula

  before and after endotoxin instillation (Day 1 to Day 2)

• Bronchoalveolar lavage (BAL) cell counts (including total nucleated and neutrophil counts)

  6 hours post-endotoxin instillation

• Number and percent of iNOS-stained BAL cells by flow cytometry

  6 hours post-endotoxin instillation

Study Arms (1)

Endotoxin and [18F](+/-)NOS

EXPERIMENTAL

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 \[18F\](+/-)NOS.

Drug: Endotoxin (E. coli O:113, Reference Endotoxin); Drug: [18F](+/-)NOS

Interventions

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

The endotoxin will be reconstituted with sterile water to a final concentration of 2,000 endotoxin units/ml. The dose of 4 ng/kg will be prepared to a final volume of 2 ml and will be administered using a 5F balloon-tipped monitoring catheter inserted via a fiberoptic bronchoscope into the lateral segment of the right middle lobe of the lung on the morning of Day 2.

Also known as: Lipopolysaccharide

Endotoxin and [18F](+/-)NOS

[18F](+/-)NOS DRUG

7 mCi of \[18F\](+/-)NOS will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition

Endotoxin and [18F](+/-)NOS

Eligibility Criteria

• Age: 19 Years - 44 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy man or woman, any race or ethnicity, age 19-44 years old
• Screening FEV1 and FVC greater than or equal to 90% of predicted
• Screening oxygen saturation by pulse oximetry greater than or equal to 97% on room air
• Capable of lying still and supine with arms raised above the head within PET/CT scanner for 2-2.5 hours
• Capable of following instructions for breathing protocol during CT portion of PET/CT scans
• Able and willing to give informed consent
• Body Mass Index (BMI) \< 35

You may not qualify if:

• Pregnancy (confirmed by qualitative serum hCG pregnancy test)
• Lactation
• 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, Penicillin, Lidocaine, Demerol, Versed, and/or Fentanyl
• Inability to lie flat for 2-2.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT
• Prior research-related radiation exposure within the past year such that participation in this study would result in exposures that exceed the limits as defined by the FDA RDRC regulations (21 CFR 361.1)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

Washington University School of Medicine / Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Pneumonia

Interventions

Endotoxins; Lipopolysaccharides; Fluorine-18

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens

Study Officials

• Delphine Chen, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: July 23, 2018

Record last verified: 2018-07

Locations

US (1)