Inflammatory conditions in general and immunosuppressive conditions is particular
Conditions
Interventions
Trade Name: Fluenz
Pharmaceutical Form: Nasal spray, solution
Product Name: Lipopolysaccharide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Lipopolysaccharide
Current S
Sponsors
Radboudumc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: -Age =18 and =35 years of age -Male -Healthy Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Pre-existent lung disease, including asthma - A history of allergic rhinitis - Use of any medication - Current smoker or more than 5 pack-year history - Use of recreational drugs within 21 days prior to start of the study - Use of caffeine or alcohol within 1 day prior to start of the study - Surgery or trauma with significant blood loss or blood donation within 3 months prior to start of the study - Participation in another clinical trial within 3 months prior to start of the study - Frequent nosebleeds - Recent nasal or otologic surgery - Clinically significant acute (febrile) illness or a common cold within four weeks prior to start of the study - History of frequent vaso-vagal collapse or of orthostatic hypotension History, signs or symptoms of cardiovascular disease. - History of allergic reaction to Fluenz™, eggs / gelatin / gentamicin - History of Guillain-Barré Syndrome - Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block. - Hypertension (defined as RR systolic > 160 or RR diastolic > 90). - Hypotension (defined as RR systolic 120 µmol/l). - Liver function abnormality: alkaline phosphatase>230 U/L and/or ALT>90 U/L - CRP > 20 mg/L, WBC > 12x109/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to investigate the effects of an endotoxin challenge and subsequent development of endotoxin tolerance on the local immune response following Fluenz™ administration in vivo. The primary outcome measure is the difference in concentrations of CXCL-10 in nasal wash between subjects in the placebo-Fluenz™ group and the LPS-Fluenz™ group.;Secondary Objective: Secondary endpoints include other local inflammatory parameters, including antibodies, immune cells, cytokines and local symptoms. Also, systemic inflammatory effects will be assessed, including circulating antibodies, immune cells and cytokines, lower respiratory tract and systemic symptoms and peak expiratory flow. Furthermore, viral shedding of influenza will be measured in nasal wash. Finally, changes in the mucosal microbiome will be assessed.;Primary end point(s): Our primary objective is to investigate the effects of endotoxin-induced systemic inflammation and subsequent development of endotoxin tolerance on the inflammatory response following Fluenz™ administration in vivo. To evaluate whether these effects involve local and/or systemic inflammation, symptoms, temperature and peak expiratory flow will be measured. Next, local inflammatory parameters are measured in nasal wash and systemic inflammatory parameters are measured in blood. Furthermore, we want to evaluate whether preceding endotoxemia influences the viral shedding of influenza in nasal wash. Finally, changes in the mucosal microbiome will be assessed.;Timepoint(s) of evaluation of this end point: Timepoints in minutes relative to LPS administration: T= -90, -60, 0, 60, 90, 120, 180, 240, 360, 480 and in days post-LPS administration: D=7, 8,9, 10, 11, 14, 21, 35 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Other cytokines / chemokines in nasal wash -Influenza viral shedding in nasal wash -Leukocyte numbers and differentiation in nasal wash -Fluenz™ antibodies (IgA) in nasal wash (measured for all three subtypes H1N1, H3N2, B). -Circulating leukocyte counts and differentiation -Plasma cytokines -Fluenz™ antibodies (IgG) in serum. -Cytokine production by leukocytes ex vivo stimulated with various pathogens/stimuli. -Body temperature. -Hemodynamic parameters -symptoms Peak expiratory flow (PEF). Mucosal microbiome. ;Timepoint(s) of evaluation of this end point: Timepoints in minutes relative to LPS administration: T= -90, -60, 0, 60, 90, 120, 180, 240, 360, 480 and in days post-LPS administration: D=7, 8,9, 10, 11, 14, 21, 35 | — |
Countries
Netherlands
Contacts
Public ContactResearch IC, office of Rebecca Koch
Radboudumc
Outcome results
None listed