Inflammatory Markers in Sputum After LPS Inhalation

Sponsor

Centre Hospitalier Universitaire Brugmann (Other)

Overall Status

Unknown status

CT.gov ID

NCT01081392

Collaborator

(none)

Enrollment

Location

Arms

3.9

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammation	Biological: LPS	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

The Role of Inhaled Particle Size on the Inflammatory Response Induced by Endotoxin Inhalation

Study Start Date :

Jan 1, 2010

Anticipated Primary Completion Date :

Apr 1, 2010

Anticipated Study Completion Date :

May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LPS sequence 1 Nebulizers A then B then C	Biological: LPS LPS 20mcg sd inhaled via nebulizer, 3 periods
Experimental: LPS sequence 2 Nebulizers B then C then A	Biological: LPS LPS 20mcg sd inhaled via nebulizer, 3 periods
Experimental: LPS sequence 3 Nebulizers C then A then B	Biological: LPS LPS 20mcg sd inhaled via nebulizer, 3 periods
Experimental: LPS sequence 4 Nebulizers A then C then B	Biological: LPS LPS 20mcg sd inhaled via nebulizer, 3 periods
Experimental: LPS sequence 5 Nebulizers C then B then A	Biological: LPS LPS 20mcg sd inhaled via nebulizer, 3 periods
Experimental: LPS sequence 6 Nebulizers B then A then C	Biological: LPS LPS 20mcg sd inhaled via nebulizer, 3 periods

Outcome Measures

Primary Outcome Measures

Absolute neutrophil count in sputum [24hrs after LPS inhalation]

Secondary Outcome Measures

white blood cells and differential in peripheral blood [0, 6 and 24 hrs after LPS inhalation]
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]
Alveolo-capillary diffusion [0, 6 and 24hrs 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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