Inflammation
Conditions
Keywords
LPS, endotoxin, inflammatory markers, healthy volunteers, neutrophils in sputum
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.
Interventions
BIOLOGICALLPS
LPS 20mcg sd inhaled via nebulizer, 3 periods
Sponsors
Centre Hospitalier Universitaire Brugmann
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute neutrophil count in sputum | 24hrs after LPS inhalation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CC16 in peripheral blood | 0, 6 and 24hrs after LPS inhalation | — |
| Calgranulin A/B | 0, 6 and 24hrs after LPS inhalation | — |
| CRP in peripheral blood | 0, 6 and 24hrs after LPS inhalation | — |
| Spirometry (FEV1 and FEV1/FEV) | 0, 1, 6 and 24hrs after LPS inhalation | — |
| white blood cells and differential in peripheral blood | 0, 6 and 24 hrs after LPS inhalation | — |
| 12-lead ECG | Screening Visit 1 and final Visit 5 | — |
| Physical exam | At the Screening Visit 1, at the three Visits with LPS inhalation and at the Final Visit | A complete physical exam at screening and at the final Visits, and an abbreviated physical exam at the three Visits during which LPS will be administered |
| Safety labs from peripheral blood | At the Screening Visit 1 and the Final Visit 5 | hematology, blood chemistry (ionogram, AST, ALT, alkaline phosphatases, urea, creatinine) |
| Alveolo-capillary diffusion | 0, 6 and 24hrs after LPS inhalation | — |
Countries
Belgium
Outcome results
None listed