Clinical trial NCT00741013: Quantifying Airway Inflammation With Radiologic Tests
Official title: Imaging Biomarkers of Pulmonary Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Lung Inflammation
Keywords: randomized
positron emission tomography
lung inflammation
lovastatin
recombinant human activated protein C
endotoxin
fluorodeoxyglucose
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Barnes-Jewish Hospital
First posted: 2008-08-25
Enrollment: 22
Sex: ALL
Minimum age (years): 19
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

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 \<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.

Primary outcomes:
measure: Change in Ki (Measure of [18F]Fluorodeoxyglucose ([18F]FDG) Uptake Determined by Patlak Graphical Analysis) in the Right Lung 24 Hours After LPS Instillation
timeFrame: 24 hours after endotoxin instillation
Secondary outcomes:
measure: Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation
timeFrame: 24 hours after endotoxin instillation
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Delphine L Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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;180(6):533-9. doi: 10.1164/rccm.200904-0501OC. Epub 2009 Jul 2.