Lung InflammationEarly Phase 1NCT00741013
Quantifying Airway Inflammation With Radiologic Tests
A Early Phase 1 study testing Endotoxin in people with Lung Inflammation, run by Washington University School of Medicine at 1 site in United States.
Trial summary
In this randomized, double-blind, placebo controlled trial we used positron emission tomography to determine if lovastatin or recombinant human activated protein C exhibit anti-inflammatory effects in humans following intrabronchial installation of lipopolysaccharide (LPS or endotoxin). 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
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Mar 2008
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 must be > 80% of predicted.
- Screening oxygen saturation by pulse oximetry is >97% on room air.
- Research volunteer must be capable of lying still and supine within the PET scanner for ~2 ½ hours.
- Research volunteer must be capable of fasting for 6 hours.
Who cannot join
- Pregnancy (confirmed by a qualitative urine hCG pregnancy test)
- Lactation.
- Actively menstruating at time of randomization
- History of tobacco use or has smoked other illicit drugs (marijuana, cocaine) in the past year.
- Research volunteer is currently taking any prescription medications.
- Research volunteer is at increased risk for radiation exposure (e.g. flight attendants)
Show all 30Show fewer
- Research volunteer is enrolled in another research study of an investigational drug.
- Research volunteer has a known allergy to both trimethoprim/sulfamethoxazole and amoxicillin.
- Research volunteer has a known allergy to drugs routinely used during bronchoscopy.
- Research volunteer has a known allergy to lovastatin or rhAPC
- Fasting glucose at time of PET study > 150 mg/dl.
- Active or history of internal bleeding within the past 3 months
- History of hemorrhagic stroke within the past 3 months.
- History of intracranial or intraspinal surgery, or severe head trauma, within the past 3 months
- History of trauma with an increased risk of life-threatening bleeding within the past 3 months
- History of receiving thrombolytic therapy within the past 3 months.
- History of receiving oral anticoagulants or glycoprotein IIb/IIIa inhibitors within the past 3 months.
- History of using aspirin > 650 mg/d or other platelet inhibitors within the past 7 days.
- Any history of intracranial arteriovenous malformation or aneurysm
- Any history of a known bleeding diathesis
- Any history of chronic severe hepatic disease
- Presence of an epidural catheter
- Any history of intracranial neoplasm or mass lesion or evidence of cerebral herniation
- Use of heparin during past 7 days
- Platelet count <100,000 x 106/L
- Prothrombin time-INR > 1.5
- SGOT >47 IU/L, SGPT > 53 IU/L, or bilirubin > 1.1 mg/dl
- Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.
- History of chronic active liver disease or acute liver disease within the past 3 months
- SGOT >47 IU/L, SGPT > 53 IU/L, or bilirubin > 1.1 mg/dl.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Imaging Biomarkers of Pulmonary Inflammation
In this randomized, double-blind, placebo controlled trial we used positron emission tomography to determine if lovastatin or recombinant human activated protein C exhibit anti-inflammatory effects in humans following intrabronchial installation of lipopolysaccharide (LPS or endotoxin).
Read the detailed description
Quantitative, noninvasive biomarkers for lung-specific inflammation have yet to be developed but can potentially contribute significantly to the development of therapies to treat lung inflammation. The purpose of this study was to demonstrate that positron emission tomographic (PET) imaging with [18F}fluorodeoxyglucose (FDG-PET) can be used to quantify the change in lung inflammation in healthy volunteers.
- Conditions
- Lung Inflammation
- Being tested
- placebo pill and placebo IV, Lovastatin pill and placebo IV, placebo pill and recombinant human activated protein C IV, Endotoxin
- Keywords
- randomized, positron emission tomography, lung inflammation, lovastatin, recombinant human activated protein C, endotoxin, fluorodeoxyglucose
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placebo pill and placebo IVDrug
Placebo pill every four hours, starting 16 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS
Placebo IV starting 2 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS
Lovastatin pill and placebo IVDrug
Also called Mevacor
lovastatin pill every four hours, total of 80 milligrams a day, starting 16 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS
Placebo IV starting 2 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS
placebo pill and recombinant human activated protein C IVDrug
Also called Xigris
placebo pill every four hours, total of 80 milligrams a day, starting 16 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS
recombinant human activated protein C IV 24 micrograms per kg per hour starting 2 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS
EndotoxinBiological
Also called Reference Endotoxin (E. Coli O113:H10K), lipopolysaccharide
Endotoxin 4 ng/kg instilled bronchoscopically in all volunteers 12 hours after starting lovastatin treatment and 2 hours after starting recombinant human activated protein C treatment.
| Study group | Role | What they receive |
|---|---|---|
| Placebo pill and placebo IV | Placebo comparator | Not described Receives: Drug: placebo pill and placebo IV; Biological: Endotoxin |
| Lovastatin pill and placebo IV | Experimental | Not described Receives: Drug: Lovastatin pill and placebo IV; Biological: Endotoxin |
| Placebo pill and rhAPC IV | Experimental | Not described Receives: Drug: placebo pill and recombinant human activated protein C IV; Biological: Endotoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation
Calculated Ki was used to measure the amount of lung inflammation before and after instillation of endotoxin to assess the effect of placebo, lovastatin, and rhAPC treatment
Measured: 24 hours after endotoxin instillation
Secondary outcomes (1)
Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation
Number of total nucleated cells isolated from the first aliquoe of BAL obtained to correlate with PET data.
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 posted25 Aug 2008 (estimated)
- Study startMar 2007
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung InflammationStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Barnes-Jewish Hospital
- Responsible party
- Sponsor
- Investigators
- Delphine L Chen, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00741013
- Sponsor's protocol ID
- 05-1137
- Status last verified
- Apr 2014
- First submitted
- 21 Aug 2008
- Last updated
- 26 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chen DL, Bedient TJ, Kozlowski J, Rosenbluth DB, Isakow W, Ferkol TW, Thomas B, Mintun MA, Schuster DP, Walter MJ. [18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation. Am J Respir Crit Care Med. 2009 Sep 15;180(6):533-9. doi: 10.1164/rccm.200904-0501OC. Epub 2009 Jul 2.
PubMed 19574441
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging Biomarkers of Pulmonary Inflammation
- ClinicalTrials.gov ID
- NCT00741013
- Acronym / sponsor ID
- 05-1137
- Conditions
- Lung Inflammation
- Keywords
- randomized, positron emission tomography, lung inflammation, lovastatin, recombinant human activated protein C, endotoxin, fluorodeoxyglucose
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Barnes-Jewish Hospital
- Study start
- Mar 2007
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 25 Aug 2008 (estimated)
- Results
- Posted 26 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this randomized, double-blind, placebo controlled trial we used positron emission tomography to determine if lovastatin or recombinant human activated protein C exhibit anti-inflammatory effects in humans following intrabronchial installation of lipopolysaccharide (LPS or endotoxin).
Detailed description
Quantitative, noninvasive biomarkers for lung-specific inflammation have yet to be developed but can potentially contribute significantly to the development of therapies to treat lung inflammation. The purpose of this study was to demonstrate that positron emission tomographic (PET) imaging with [18F}fluorodeoxyglucose (FDG-PET) can be used to quantify the change in lung inflammation in healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo pill and placebo IV | Placebo comparator | Drug: placebo pill and placebo IV, Biological: Endotoxin |
| Lovastatin pill and placebo IV | Experimental | Drug: Lovastatin pill and placebo IV, Biological: Endotoxin |
| Placebo pill and rhAPC IV | Experimental | Drug: placebo pill and recombinant human activated protein C IV, Biological: Endotoxin |
Who may qualify
- Ages
- 19 to 44 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy, man or woman, any race or ethnicity, age 19 - 44 years old
- Screening FEV1 and FVC must be > 80% of predicted.
- Screening oxygen saturation by pulse oximetry is >97% on room air.
- Research volunteer must be capable of lying still and supine within the PET scanner for ~2 ½ hours.
- Research volunteer must be capable of fasting for 6 hours.
Key exclusion criteria (30 listed)
- Pregnancy (confirmed by a qualitative urine hCG pregnancy test)
- Lactation.
- Actively menstruating at time of randomization
- History of tobacco use or has smoked other illicit drugs (marijuana, cocaine) in the past year.
- Research volunteer is 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 |
|---|---|---|
| placebo pill and placebo IVPlacebo pill every four hours, starting 16 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS Placebo IV starting 2 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS | Drug | Placebo pill and placebo IV |
| Lovastatin pill and placebo IVAlso: Mevacorlovastatin pill every four hours, total of 80 milligrams a day, starting 16 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS Placebo IV starting 2 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS | Drug | Lovastatin pill and placebo IV |
| placebo pill and recombinant human activated protein C IVAlso: Xigrisplacebo pill every four hours, total of 80 milligrams a day, starting 16 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS recombinant human activated protein C IV 24 micrograms per kg per hour starting 2 hours before intrabronchial LPS and ending 24 hours after intrabronchial LPS | Drug | Placebo pill and rhAPC IV |
| EndotoxinAlso: Reference Endotoxin (E. Coli O113:H10K), lipopolysaccharideEndotoxin 4 ng/kg instilled bronchoscopically in all volunteers 12 hours after starting lovastatin treatment and 2 hours after starting recombinant human activated protein C treatment. | Biological | Lovastatin pill and placebo IV, Placebo pill and placebo IV, Placebo pill and rhAPC IV |
Primary outcome
Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation
Time frame: 24 hours after endotoxin instillation
Calculated Ki was used to measure the amount of lung inflammation before and after instillation of endotoxin to assess the effect of placebo, lovastatin, and rhAPC treatment
1 secondary outcome
Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation
Time frame: 24 hours after endotoxin instillation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19574441Chen DL, Bedient TJ, Kozlowski J, Rosenbluth DB, Isakow W, Ferkol TW, Thomas B, Mintun MA, Schuster DP, Walter MJ. [18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation. Am J Respir Crit Care Med. 2009 Sep 15;180(6):533-9. doi: 10.1164/rccm.200904-0501OC. Epub 2009 Jul 2.
Related trials for Lung Inflammation
RecruitingPhase 2
Rademikibart IV for Acute Asthma and COPD Exacerbation
Asthma Acute, COPD Exacerbation Acute
RecruitingObservational study
Comparison of Cardiac Index Measurement Using Right Ventricular Pressure Curve Analysis and Thermodilution Via a Swan-Ganz IQ™ Catheter.
Septic Shock
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Enrolling by invitationPhase 2
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
Systemic Inflammation, Neuroinflammation
Not yet recruitingObservational study
Type 2 Inflammation in Adults With Cystic Fibrosis
Cystic Fibrosis (CF), Type 2 Inflammatory Disorders
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 Early Phase 1 study testing Endotoxin 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 5 inclusion and 30 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 26 May 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 26 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation (time frame: 24 hours after endotoxin instillation). 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 NCT00741013, 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 26 May 2014.