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Quantifying Airway Inflammation With Radiologic Tests
This study has been completed.
Sponsor:
Washington University School of Medicine
Collaborator:
Barnes-Jewish Hospital
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00741013
First received: August 21, 2008
Last updated: April 22, 2014
Last verified: April 2014
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
| Lung Inflammation | Drug: placebo pill and placebo IV Drug: Lovastatin pill and placebo IV Drug: placebo pill and recombinant human activated protein C IV Biological: Endotoxin | Early Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Imaging Biomarkers of Pulmonary Inflammation |
Resource links provided by NLM:
Further study details as provided by Washington University School of Medicine:
Primary Outcome Measures:
- 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
Secondary Outcome Measures:
- Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation [ Time Frame: 24 hours after endotoxin instillation ]Number of total nucleated cells isolated from the first aliquoe of BAL obtained to correlate with PET data.
| Enrollment: | 22 |
| Study Start Date: | March 2007 |
| Study Completion Date: | March 2008 |
| Primary Completion Date: | March 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Placebo Comparator: Placebo pill and placebo IV |
Drug: placebo pill and placebo IV
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 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.
Other Names:
|
| Experimental: Lovastatin pill and placebo IV |
Drug: Lovastatin pill and placebo IV
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 Other Name: Mevacor
Biological: Endotoxin
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.
Other Names:
|
| Experimental: Placebo pill and rhAPC IV |
Drug: placebo pill and recombinant human activated protein C IV
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 Other Name: Xigris
Biological: Endotoxin
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.
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 19 Years to 44 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- 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.
-
Exclusion criteria related to use of rhAPC:
- 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.
-
Exclusion criteria related to use of lovastatin:
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00741013
Please refer to this study by its ClinicalTrials.gov identifier: NCT00741013
Locations
| United States, Missouri | |
| Washington University School of Medicine | |
| Saint Louis, Missouri, United States, 63110 | |
Sponsors and Collaborators
Washington University School of Medicine
Barnes-Jewish Hospital
Investigators
| Principal Investigator: | Delphine L Chen, MD | Washington University School of Medicine |
More Information
Publications:
| Responsible Party: | Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00741013 History of Changes |
| Other Study ID Numbers: |
05-1137 |
| Study First Received: | August 21, 2008 |
| Results First Received: | August 4, 2009 |
| Last Updated: | April 22, 2014 |
Keywords provided by Washington University School of Medicine:
|
randomized positron emission tomography lung inflammation lovastatin |
recombinant human activated protein C endotoxin fluorodeoxyglucose |
Additional relevant MeSH terms:
|
Inflammation Pneumonia Pathologic Processes Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections Lovastatin L 647318 Dihydromevinolin Protein C Drotrecogin alfa activated |
Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on July 25, 2017