Quantifying Airway Inflammation With Radiologic Tests
Primary Purpose
Lung Inflammation
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
placebo pill and placebo IV
Lovastatin pill and placebo IV
placebo pill and recombinant human activated protein C IV
Endotoxin
Sponsored by
About this trial
This is an interventional treatment trial for Lung Inflammation focused on measuring randomized, positron emission tomography, lung inflammation, lovastatin, recombinant human activated protein C, endotoxin, fluorodeoxyglucose
Eligibility 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.
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo pill and placebo IV
Lovastatin pill and placebo IV
Placebo pill and rhAPC IV
Arm Description
Outcomes
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
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
Number of total nucleated cells isolated from the first aliquoe of BAL obtained to correlate with PET data.
Full Information
NCT ID
NCT00741013
First Posted
August 21, 2008
Last Updated
April 22, 2014
Sponsor
Washington University School of Medicine
Collaborators
Barnes-Jewish Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00741013
Brief Title
Quantifying Airway Inflammation With Radiologic Tests
Official Title
Imaging Biomarkers of Pulmonary Inflammation
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Barnes-Jewish Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Inflammation
Keywords
randomized, positron emission tomography, lung inflammation, lovastatin, recombinant human activated protein C, endotoxin, fluorodeoxyglucose
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo pill and placebo IV
Arm Type
Placebo Comparator
Arm Title
Lovastatin pill and placebo IV
Arm Type
Experimental
Arm Title
Placebo pill and rhAPC IV
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
placebo pill and placebo IV
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Lovastatin pill and placebo IV
Other Intervention Name(s)
Mevacor
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
placebo pill and recombinant human activated protein C IV
Other Intervention Name(s)
Xigris
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Endotoxin
Other Intervention Name(s)
Reference Endotoxin (E. Coli O113:H10K), lipopolysaccharide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation
Description
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
Time Frame
24 hours after endotoxin instillation
Secondary Outcome Measure Information:
Title
Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation
Description
Number of total nucleated cells isolated from the first aliquoe of BAL obtained to correlate with PET data.
Time Frame
24 hours after endotoxin instillation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
44 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Delphine L Chen, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
19574441
Citation
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.
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