Quantifying Airway Inflammation With Radiologic Tests

April 22, 2014 updated by: Washington University School of Medicine

Imaging Biomarkers of Pulmonary Inflammation

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 44 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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

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.
Other Names:
  • lipopolysaccharide
  • Reference Endotoxin (E. Coli O113:H10K)
Experimental: Lovastatin pill and placebo IV
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.
Other Names:
  • lipopolysaccharide
  • Reference Endotoxin (E. Coli O113:H10K)
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 Names:
  • Mevacor
Experimental: Placebo pill and rhAPC IV
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.
Other Names:
  • lipopolysaccharide
  • Reference Endotoxin (E. Coli O113:H10K)
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 Names:
  • Xigris

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation
Time Frame: 24 hours after endotoxin 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Barnes-Jewish Hospital

Investigators

  • Principal Investigator: Delphine L Chen, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

August 21, 2008

First Submitted That Met QC Criteria

August 22, 2008

First Posted (Estimate)

August 25, 2008

Study Record Updates

Last Update Posted (Estimate)

May 26, 2014

Last Update Submitted That Met QC Criteria

April 22, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-1137

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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