Quantifying Airway Inflammation With Radiologic Tests

• Status: Completed
• Trial end date: 2008-03-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: Barnes-Jewish Hospital
• Treatments: Dihydromevinolin; Drotrecogin alfa activated; L 647318; Lovastatin; Protein C

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.