NCT00741013

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Mar 2007

Shorter than P25 for early_phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2007

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2008

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

August 21, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 25, 2008

Completed
5.8 years until next milestone

Results Posted

Study results publicly available

May 26, 2014

Completed
Last Updated

May 26, 2014

Status Verified

April 1, 2014

Enrollment Period

1 year

First QC Date

August 21, 2008

Results QC Date

August 4, 2009

Last Update Submit

April 22, 2014

Conditions

Lung Inflammation

Keywords

randomizedpositron emission tomographylung inflammationlovastatinrecombinant human activated protein Cendotoxinfluorodeoxyglucose

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • Number of Total Nucleated Cells From Bronchoalveolar Lavage (BAL) Fluid 24 Hours After Endotoxin Instillation

    24 hours after endotoxin instillation

Study Arms (3)

Placebo pill and placebo IV

PLACEBO COMPARATOR
Drug: placebo pill and placebo IVBiological: Endotoxin

Lovastatin pill and placebo IV

EXPERIMENTAL
Drug: Lovastatin pill and placebo IVBiological: Endotoxin

Placebo pill and rhAPC IV

EXPERIMENTAL
Drug: placebo pill and recombinant human activated protein C IVBiological: Endotoxin

Interventions

placebo pill and placebo IVDRUG

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

Placebo pill and placebo IV
Lovastatin pill and placebo IVDRUG

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

Also known as: Mevacor
Lovastatin pill and placebo IV
placebo pill and recombinant human activated protein C IVDRUG

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

Also known as: Xigris
Placebo pill and rhAPC IV
EndotoxinBIOLOGICAL

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.

Also known as: Reference Endotoxin (E. Coli O113:H10K), lipopolysaccharide
Lovastatin pill and placebo IVPlacebo pill and placebo IVPlacebo pill and rhAPC IV

Eligibility Criteria

Age19 Years - 44 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related 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;180(6):533-9. doi: 10.1164/rccm.200904-0501OC. Epub 2009 Jul 2.

    PMID: 19574441RESULT

MeSH Terms

Conditions

Pneumonia

Interventions

Lovastatindrotrecogin alfa activatedEndotoxinsLipopolysaccharides

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

NaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsBacterial ToxinsToxins, BiologicalBiological FactorsGlycoconjugatesCarbohydratesPolysaccharides, BacterialPolysaccharidesLipidsAntigens, BacterialAntigens

Results Point of Contact

Title
Delphine L. Chen
Organization
Washington University School of Medicine
chend@mir.wustl.edu
314-362-7029

Study Officials

  • Delphine L Chen, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2008

First Posted

August 25, 2008

Study Start

March 1, 2007

Primary Completion

March 1, 2008

Study Completion

March 1, 2008

Last Updated

May 26, 2014

Results First Posted

May 26, 2014

Record last verified: 2014-04

Locations

US(1)