Possible future indications: infectious diseases which require vasopressor therapy.
Conditions
Interventions
Trade Name: Noradrenaline
Product Name: Noradrenaline
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: In
Sponsors
Radboudumc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Written informed consent - Age =18 and =35 yrs - 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 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Use of any medication - Smoking - Previous spontaneous vagal collapse - History of atrial or ventricular arrhythmia - (Family) history of myocardial infarction or stroke under the age of 65 years - 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 enzyme abnormalities or positive hepatitis serology - Medical history of any disease associated with immune deficiency - CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxin administration - Participation in a drug trial or donation of blood 3 months prior to the LPS challenge - Use of recreational drugs within 7 days prior to experiment day - Recent hospital admission or surgery with general anaesthesia (<3 months)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to investigate whether noradrenaline exerts immunomodulatory effects in humans in vivo during experimental human endotoxemia. (administration of lipopolysaccharide [LPS] in healthy volunteers).;Secondary Objective: Secondary objectives include 1) To determine the extent of immunomodulatory effects of phenylephrine and vasopressin in humans in vivo during experimental human endotoxemia. (administration of lipopolysaccharide [LPS] in healthy volunteers). 2) To determine the effects of the different vasopressors on responsiveness of leukocytes to various inflammatory stimuli ex vivo. 3) To determine the effects of the different vasopressors on the phenotype of circulating leukocytes. 4) To determine the effects of the different vasopressors on inflammatory transcriptional pathways, and 5) To determine the effects of the different vasopressors on LPS-induced clinical symptoms (illness score) and hemodynamic/temperature changes. ;Primary end point(s): The primary study endpoint is the difference in the time-course of LPS-induced TNF-a plasma concentrations following endotoxemia between the noradrenaline and the placebo groups.;Timepoint(s) of evaluation of this end point: Timepoints are minutes relative to LPS administration: -45; 0; 30; 60; 90; 120; 180; 240; 360; 480 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Differences between groups in: - Various other inflammatory cytokines, including but not limited to IL-10 and IL-6 - Ex vivo production of inflammatory mediators by stimulated leukocytes - The phenotype of circulating leukocytes - Inflammatory transcriptional pathways (by use of qPCR/microarrays/RNA sequencing) - Illness score - Mean arterial pressure - Heart rate - Temperature;Timepoint(s) of evaluation of this end point: Timepoints are minutes relative to LPS administration: -45; 0; 30; 60; 90; 120; 180; 240; 360; 480 | — |
Countries
Netherlands
Contacts
Public ContactResearch IC, office of Roel Stolk
Radboudumc
Outcome results
None listed