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Early Phase 1 N=22 Randomized Quadruple-blind Treatment

Quantifying Airway Inflammation With Radiologic Tests

Lung Inflammation

Enrolled (actual)
22
Serious AEs
4.6%
Results posted
May 2014
Primary outcome: Primary: Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation — 18.8; 8.4; 14.2 Change in Ki — p=<0.05

Study Design & Population

Study type
Interventional
Phase
Early Phase 1
Interventions
placebo pill and placebo IV (Drug); Lovastatin pill and placebo IV (Drug); placebo pill and recombinant human activated protein C IV (Drug); Endotoxin (Biological)
Age
Adult · 19+ yrs
Sex
All
Sponsor
Washington University School of Medicine
Primary completion
Mar 2008

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation
18.8; 8.4; 14.2 <0.05 sig
SECONDARY
Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation
545; 311; 520

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).

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 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00741013). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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