Quantifying Airway Inflammation With Radiologic Tests

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Barnes-Jewish Hospital
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00741013
First received: August 21, 2008
Last updated: August 22, 2008
Last verified: August 2008
  Purpose

In this randomized, double-blind, placebo controlled trial we will utilize 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
Inflammation
Drug: placebo pill and placebo IV
Drug: lovastatin pill and placebo IV
Drug: placebo pill and recombinant human activated protein C IV

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:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • [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 ]

Secondary Outcome Measures:
  • Bronchoalveolar lavage total cells, cell differential and IL-8 concentrations [ Time Frame: After intrabronchial installation of LPS ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: March 2007
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
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

Experimental: 2
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
Experimental: 3
Placebo pill and recombinant human activated protein C 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

  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 instraspinal 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
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: Micahel J Walter, MD Washington University School of Medicine
  More Information

No publications provided by Washington University School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael J. Walter, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00741013     History of Changes
Other Study ID Numbers: 05-1137
Study First Received: August 21, 2008
Last Updated: August 22, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
randomized
positron emission tomography
inflammation
lovastatin
recombinant human activated protein C
attenuate
endotoxin-dependent

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

ClinicalTrials.gov processed this record on April 17, 2014