PneumoniaPhase 1NCT01407796
PET Imaging of Endotoxin-induced iNOS Activation
A Phase 1 study testing Endotoxin (E. coli O:113, Reference Endotoxin) and [18F](+/-)NOS in people with Pneumonia, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 44 yearsHealthy volunteers can take part
- Conditions the study is for
- Pneumonia
- What is being tested?
- Endotoxin (E. coli O:113, Reference Endotoxin) and [18F](+/-)NOS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Apr 2012
- Phase
- 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 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicne
St Louis, Missouri, 63110
About this study
Official title: PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers
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.
Read the 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
- Being tested
- Endotoxin (E. coli O:113, Reference Endotoxin), [18F](+/-)NOS
- Keywords
- lung inflammation, positron emission tomography (PET), fluorodeoxyglucose (FDG), inducible nitric oxide synthase (iNOS), lung anti-inflammatory therapy
- 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
[18F](+/-)NOSDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 F-18 (+/-) 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.
Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe.
Measured: Change in DVR on post-endotoxin scan (Day 2) from baseline (Day 1).
Secondary outcomes (2)
Bronchoalveolar lavage (BAL) fluid cell counts.
Total nucleated and neutrophil cell counts obtained by BAL after endotoxin instillation.
Measured: 24 hours after endotoxin instillation.
Number and percent of iNOS-stained BAL cells.
Measured: 24 hours after endotoxin instillation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2011 (estimated)
- Study startDec 2010
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Barnes-Jewish Hospital
- Responsible party
- Principal investigator, Delphine L. Chen, MD, Washington University School of Medicine
- Investigators
- Delphine L. Chen, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01407796
- Sponsor's protocol ID
- BJHF/ICTS 7326-01
- Status last verified
- Apr 2014
- First submitted
- 28 Jul 2011
- Last updated
- 21 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25525182
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01407796
- Acronym / sponsor ID
- BJHF/ICTS 7326-01
- Conditions
- Pneumonia
- Keywords
- lung inflammation, positron emission tomography (PET), fluorodeoxyglucose (FDG), inducible nitric oxide synthase (iNOS), lung anti-inflammatory therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Barnes-Jewish Hospital
- Study start
- Dec 2010
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 2 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Endotoxin and [18F](+/-)NOS | Experimental | Drug: Endotoxin (E. coli O:113, Reference Endotoxin), Drug: [18F](+/-)NOSAll 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 |
Who may qualify
- Ages
- 19 to 44 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- Pregnancy (confirmed by qualitative serum hCG pregnancy test)
- Lactation
- Active menstruation
- History of cardiopulmonary disease
- Currently taking any prescription medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endotoxin (E. coli O:113, Reference Endotoxin)Also: Lipopolysaccharide | Drug | Endotoxin and [18F](+/-)NOS |
| [18F](+/-)NOS | Drug | Endotoxin and [18F](+/-)NOS |
Primary outcome
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).
2 secondary outcomes
Bronchoalveolar lavage (BAL) fluid cell counts.
Time frame: 24 hours after endotoxin instillation.
Number and percent of iNOS-stained BAL cells.
Time frame: 24 hours after endotoxin instillation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2014.
- Derived from this study: PubMed 25525182Huang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Delphine L. Chen, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Endotoxin (E. coli O:113, Reference Endotoxin) and [18F](+/-)NOS in people with Pneumonia, 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 11 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 21 Apr 2014. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 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 NCT01407796, which also lists 1 linked publication.
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 21 Apr 2014.