Quantifying Airway Inflammation With Radiologic Tests

This study has been completed.
Sponsor:
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

August 21, 2008
April 22, 2014
March 2007
March 2008   (final data collection date for 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 ] [ Designated as safety issue: No ]
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
[18F]fluorodeoxyglucose (FDG) uptake measured by positron emission tomography (PET) imaging [ Time Frame: Before and after intrabronchial installation of LPS ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00741013 on ClinicalTrials.gov Archive Site
Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation [ Time Frame: 24 hours after endotoxin instillation ] [ Designated as safety issue: No ]
Number of total nucleated cells isolated from the first aliquoe of BAL obtained to correlate with PET data.
Bronchoalveolar lavage total cells, cell differential and IL-8 concentrations [ Time Frame: After intrabronchial installation of LPS ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Quantifying Airway Inflammation With Radiologic Tests
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).

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.

Interventional
Phase 0
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Lung Inflammation
  • 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

  • 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
  • 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
  • Placebo Comparator: Placebo pill and placebo IV
    Interventions:
    • Drug: placebo pill and placebo IV
    • Biological: Endotoxin
  • Experimental: Lovastatin pill and placebo IV
    Interventions:
    • Drug: Lovastatin pill and placebo IV
    • Biological: Endotoxin
  • Experimental: Placebo pill and rhAPC IV
    Interventions:
    • Drug: placebo pill and recombinant human activated protein C IV
    • Biological: Endotoxin
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. Epub 2009 Jul 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
March 2008
March 2008   (final data collection date for primary outcome measure)

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.
Both
19 Years to 44 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00741013
05-1137
Yes
Washington University School of Medicine
Washington University School of Medicine
Barnes-Jewish Hospital
Principal Investigator: Delphine L Chen, MD Washington University School of Medicine
Washington University School of Medicine
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP