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Quantifying Airway Inflammation With Radiologic Tests

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00741013
First Posted: August 25, 2008
Last Update Posted: May 26, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Barnes-Jewish Hospital
Information provided by (Responsible Party):
Washington University School of Medicine
  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: Quadruple (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

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:
  • Reference Endotoxin (E. Coli O113:H10K)
  • lipopolysaccharide
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:
  • Reference Endotoxin (E. Coli O113:H10K)
  • lipopolysaccharide
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:
  • Reference Endotoxin (E. Coli O113:H10K)
  • lipopolysaccharide

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

Information from the National Library of Medicine

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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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
First Submitted: August 21, 2008
First Posted: August 25, 2008
Results First Submitted: August 4, 2009
Results First Posted: May 26, 2014
Last Update Posted: May 26, 2014
Last Verified: April 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