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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00741013
Other study ID # 05-1137
Secondary ID
Status Completed
Phase Phase 0
First received August 21, 2008
Last updated April 22, 2014
Start date March 2007
Est. completion date March 2008

Study information

Verified date April 2014
Source Washington University School of Medicine
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 22
Est. completion date March 2008
Est. primary completion date March 2008
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 19 Years to 44 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

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
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
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
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.

Locations

Country Name City State
United States Washington University School of Medicine Saint Louis Missouri

Sponsors (2)

Lead Sponsor Collaborator
Washington University School of Medicine Barnes-Jewish Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

Chen DL, Bedient TJ, Kozlowski J, Rosenbluth DB, Isakow W, Ferkol TW, Thomas B, Mintun MA, Schuster DP, Walter MJ. [18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation. Am J Respir Crit Care Med. 2009 Sep 15;1 — View Citation

Outcome

Type Measure Description Time frame Safety issue
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 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 24 hours after endotoxin instillation No
Secondary Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation Number of total nucleated cells isolated from the first aliquoe of BAL obtained to correlate with PET data. 24 hours after endotoxin instillation No
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