Clinical trial NCT01081392: Inflammatory Markers in Sputum After LPS Inhalation
Official title: The Role of Inhaled Particle Size on the Inflammatory Response Induced by Endotoxin Inhalation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Inflammation
Keywords: LPS
endotoxin
inflammatory markers
healthy volunteers
neutrophils in sputum
Lead sponsor: Centre Hospitalier Universitaire Brugmann
Sponsor class: OTHER
First posted: 2010-03-05
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to measure inflammatory biomarkers in sputum and peripheral blood in healthy volunteers after inhalation of single doses of LPS (20 mcg) administered as particles of different sizes.

Detailed description: Endotoxins are inflammatory substances present in the environment. In man, the inhalation of the lipopolysaccharride moiety (LPS) induces measurable immune responses. With an inhaled single dose of 20 micron, the inflammatory response in man is sub-clinical. During bronchoprovocation tests with allergens, the particle size determines to a large extent the intensity of the response. the response to LPS as a function of particle size is not known and will be studied in this study.

Eligibility criteria: Inclusion Criteria:

* healthy volunteer, non-smoking or ex-smoker \>1mth and \<10packs/year
* normal ECG
* normal lab values for hematology, ionogram, AST, ALT, alk phosphatases, urea, creatinine and CRP
* FEV1/forced vital capacity \>0.7 and FEV1\>80% of predicted value
* able to produce valid sputum following induction (\>=50% viable cells, \<50% squamous cells and \<60% neutrophils)
* females must be using contraception
* written informed consent

Exclusion Criteria:

* infection within 14 days
* history of bronchial asthma
* obstructive respiratory condition with FEV1 \<70% of theoretical value

Primary outcomes:
measure: Absolute neutrophil count in sputum
timeFrame: 24hrs after LPS inhalation
Secondary outcomes:
measure: white blood cells and differential in peripheral blood
timeFrame: 0, 6 and 24 hrs after LPS inhalation
measure: CC16 in peripheral blood
timeFrame: 0, 6 and 24hrs after LPS inhalation
measure: Calgranulin A/B
timeFrame: 0, 6 and 24hrs after LPS inhalation
measure: CRP in peripheral blood
timeFrame: 0, 6 and 24hrs after LPS inhalation
measure: Spirometry (FEV1 and FEV1/FEV)
timeFrame: 0, 1, 6 and 24hrs after LPS inhalation
measure: Alveolo-capillary diffusion
timeFrame: 0, 6 and 24hrs after LPS inhalation
measure: 12-lead ECG
timeFrame: Screening Visit 1 and final Visit 5
measure: Physical exam
timeFrame: At the Screening Visit 1, at the three Visits with LPS inhalation and at the Final Visit
measure: Safety labs from peripheral blood
timeFrame: At the Screening Visit 1 and the Final Visit 5
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brugmann
Study officials:
affiliation: CHU Brugmann
name: Olivier MICHEL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Doyen V, Pilcer G, Dinh PH, Corazza F, Bernard A, Bergmann P, Lefevre N, Amighi K, Michel O. Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers. Br J Clin Pharmacol. 2016 Nov;82(5):1371-1381. doi: 10.1111/bcp.13052. Epub 2016 Jul 28.