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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
History of Changes
  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
 Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Imaging Biomarkers of Pulmonary Inflammation

Resource links provided by NLM:

U.S. FDA Resources

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 ] [ 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


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 ] [ Designated as safety issue: No ]
    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
Ages Eligible for Study:   19 Years to 44 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Health Authority: United States: Food and Drug Administration

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
Pathologic Processes
Contraceptives, Oral
Drotrecogin alfa activated
Lovastatin
Protein C
Anti-Infective Agents
Anticholesteremic Agents
Anticoagulants
Antimetabolites
Cardiovascular Agents
Contraceptive Agents
Contraceptive Agents, Female
 Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015