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Lung InflammationEarly Phase 1NCT02151552

Assessing NOS Uptake With PET Imaging in Lung Inflammation

A Early Phase 1 study testing Endotoxin (E. coli O:113, Reference Endotoxin) and [18F](+/-)NOS in people with Lung Inflammation, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 19 to 44 yearsHealthy volunteers can take part
Conditions the study is for
Lung Inflammation
What is being tested?
Endotoxin (E. coli O:113, Reference Endotoxin) and [18F](+/-)NOS
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
May 2014to Feb 2018
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 44 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine / Barnes-Jewish Hospital

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Assessing [18F](+/-)NOS Uptake With PET Imaging in Endotoxin-induced Lung Inflammation

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.

Read the detailed description

The investigators plan to use three radioactive tracers to produce the PET images for measuring lung inflammation: [18F](+/-)NOS (the F stands for fluorine and NOS stands for Nitric Oxide Synthase, which targets iNOS), O-15 carbon monoxide ([15O]CO), and O-15 water ([15O]H2O). The NOS tracer gives information specifically about lung inflammation, while the carbon monoxide and water tracers give information about whether the lung inflammation causes more blood or water to be retained in the area of lung inflammation.

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 does not spread from one part of the body to another, and cannot spread to another person), and a small area in only one lung will be affected. In order to created this state of controlled lung inflammation, the investigators plan to place a small amount of a purified bacterial substance called endotoxin into a single small section of the lung using a bronchoscope (a long, flexible narrow tube that is passed through the mouth into the airways of the lung). This use of endotoxin is considered investigational, and the investigators have received permission from the FDA to use endotoxin in this research study.

Being tested
Endotoxin (E. coli O:113, Reference Endotoxin), [18F](+/-)NOS
Keywords
lung inflammation, positron emission tomography, inducible nitric oxide synthase
Medical subject headings
Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called Lipopolysaccharide

    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.

  • [18F](+/-)NOSDrug

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

Study groups in NCT02151552
Study groupRoleWhat they receive
Endotoxin and [18F](+/-)NOSExperimentalAll 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.
Receives: Drug: Endotoxin (E. coli O:113, Reference Endotoxin); Drug: [18F](+/-)NOS

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

  1. Change in DVR in right middle lobe

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

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

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

  3. Change in HU in right middle lobe and lingula

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

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

    Measured: 6 hours post-endotoxin instillation

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

    Measured: 6 hours post-endotoxin instillation

  6. Number and percent of 3-nitrotyrosine-stained cells on biopsy

    Measured: 6 hours post-endotoxin instillation

  7. Change in exhaled nitric oxide (ENO) levels

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

  8. Regional PBF and EVLW in right middle lobe and lingula

    Measured: before and after endotoxin (Day 1 to Day 2)

  9. Number of iNOS positive cells from brushing cytospins

    Measured: 6 hours post-endotoxin instillation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2014 (estimated)
  2. Study startMay 2014
  3. Primary completionFeb 2018
  4. Study completionFeb 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02151552
Sponsor's protocol ID
DDCF 2010060-201403017
Status last verified
Jul 2018
First submitted
28 May 2014
Last updated
23 Jul 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Endotoxin (E. coli O:113, Reference Endotoxin) and [18F](+/-)NOS in people with Lung Inflammation, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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 PET scan (Day 2) from baseline (Day 1)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02151552.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2018.

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