Suitability of a Low Dose Lipopolysaccharide (LPS) Inhalation as a Challenge Model
|Healthy||Drug: LPS challenge with nebulized LPS Drug: fluticasone propionate (FP)|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
|Official Title:||A Methodological Pilot Study to Assess the Suitability of a Low Dose LPS Inhalation as a Challenge Model in Early Translational Drug Development|
- Induced sputum [ Time Frame: 6 h after the start of LPS challenge ]• neutrophil cell count
- lung function [ Time Frame: at the end of each LPS challenge and up to 24 hours ]Change of lung function directly at the end of each challenge as well as up to 24 h after the end of exposure compared with baseline
- Blood samples [ Time Frame: before and 6 h after the start of LPS challenge ]Differential cell count
- Exhaled breath [ Time Frame: 3 hours after the start of LPS challenge ]Pre-concentrated samples (30 L, 10-15 exhalations) on a specific substrate for later analysis by Gas Chromatorgraphy - Mass Spectrometry (GC-MS) or Smart-Nose and exhaled breath temperature
- Induced sputum [ Time Frame: 6 h after the start of LPS challenge ]soluble biomarkers such as but not limited to Myeloperioxidase (MPO), Surfactant Protein D (SP-D), Interleukin (IL-8)
|Study Start Date:||August 2011|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: LPS challenge and fluticasone propionate
In case LPS induced airway inflammation is reproducible, the effect of a single high dose of inhaled fluticasone propionate will be assessed after a 4-week wash-out period.
Drug: LPS challenge with nebulized LPS
20,000 EU of Clinical Center Reference Endotoxine (CCRE) will be applied by an AKITA® Jet Nebulizer under the constant supervision of the site staff.Drug: fluticasone propionate (FP)
The dosage of FP will be 2 mg. This dosage will be inhaled by 4 puffs of Flutide® forte 500 Diskus® 500 µg / dose according to the package insert.
In this study, airway inflammation will be induced by LPS inhalation. In case a neutrophilic airway inflammation can be safely induced by inhaled LPS, the LPS challenge will be repeated. If neutrophil airway inflammation after LPS challenge is reproducible LPS challenge will be repeated after pre-treatment with a single high dose of inhaled fluticasone propionate.
To determine airway inflammation, the subjects' exhaled breath will be analyzed by different techniques, and blood samples as well as induced sputum will be collected.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01400568
|Hannover, Niedersachsen, Germany, 30625|
|Principal Investigator:||Jens Hohlfeld, MD, Professor||Fraunhofer ITEM|