Quantifying Airway Inflammation With Radiologic Tests

The Washington University

Status and phase: Completed; Early Phase 1

Conditions: Lung Inflammation

Treatments: Drug: placebo pill and recombinant human activated protein C IV; Drug: placebo pill and placebo IV; Biological: Endotoxin; Drug: Lovastatin pill and placebo IV

Study type: Interventional

Funder types: Other

Identifiers

NCT00741013

05-1137

Details and patient eligibility

About

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).

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 19 to 44 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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22 participants in 3 patient groups, including a placebo group

Placebo pill and placebo IV

Placebo Comparator group

Treatment:

Biological: Endotoxin

Drug: placebo pill and placebo IV

Lovastatin pill and placebo IV

Experimental group

Treatment:

Drug: Lovastatin pill and placebo IV

Biological: Endotoxin

Placebo pill and rhAPC IV

Experimental group

Treatment:

Biological: Endotoxin

Drug: placebo pill and recombinant human activated protein C IV