Validation of a Lung Inflammation Model in Healthy Volunteers by Radiological Tools and Glucocorticoid Treatment

The purpose of this study is to investigate the local and systemic inflammatory response and haemostatic alterations in the lungs after lipopolysaccharide (LPS) instillation and to determine the feasibility of imaging techniques to quantify lung inflammation in an adapted human endotoxin instillation model.

The investigators will also explore whether glucocorticoid treatment can blunt LPS effects.

Study Overview

• Status: Completed
• Conditions: Experimental Lung Inflammation
• Intervention / Treatment: Drug: Dexamethasone; Drug: Sterile isotonic saline

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent obtained before any trial-related activities. (Trial activities are any procedure that would not have been performed during normal management of the subject).
• Nonsmoker
• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant
• If female and of childbearing potential and subjects agrees to employ adequate birth control measures (e. g. oral contraceptives, barrier method)
• Negative urine pregnancy test

Exclusion Criteria:

• Known or suspected allergy to trial product or related products
• Pregnancy or Lactation
• Treatment with an investigational drug within three weeks prior to this trial
• Participation in an LPS trial within the last 6 weeks
• Smoking
• History of relevant cardiac arrhythmia
• Preexisting open or closed angle glaucoma
• History of Osteoporosis, Cushing´s syndrome, gastro-duodenal ulcera, cardiovascular disease, vasculitis, diabetes mellitus, hypertension, brain tumor or history of neurosurgery
• Systemic tuberculosis
• Hemorrhagic diathesis
• Relevant liver or kidney dysfunction
• Regular use of medication or abuse of alcohol unless considered clinically relevant
• Use of any medication within one week prior to the first trial day
• Symptoms of a clinically relevant illness in the 3 weeks before the first trial day
• Excessive sporting activities
• Rosacea
• Subjects on Monoamine oxidase inhibitors (should be stopped for at least two to three weeks before dihydrocodeine treatment is initiate)
• Known acute or active hepatic disease within the past 3 months
• A platelet count < 100,000 x 106/L, prothrombin time > 1.5, liver enzymes> 3 times the upper normal limit
• Having received a vaccination up to 8 weeks before the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexamethasone	Drug: Dexamethasone; Two doses of 40mg dexamethasone (in 100 ml physiologic saline solution, respectively) will be administered intravenously prior to LPS instillation.
Placebo Comparator: Sterile isotonic saline	Drug: Sterile isotonic saline; two doses of 100 ml physiologic saline solution will be administered intravenously prior to LPS instillation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The effects of LPS instillation on a putative microvascular leak formation in a lung subsegment by radiologic imaging (magnetic resonance imaging, computed tomography) will be quantified.	6/24 hours after LPS Instillation

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Bernd Jilma, MD, Department of Clinical Pharmacology, Medical University of Vienna, Waehringerguertel 18-20, A-1090 Vienna, Austria

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: September 6, 2011
• First Submitted That Met QC Criteria: October 23, 2012
• First Posted (Estimate): October 26, 2012

Study Record Updates

• Last Update Posted (Estimate): April 24, 2013
• Last Update Submitted That Met QC Criteria: April 23, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Inflammation; Pneumonia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: DEXA - LIM