Possible future indications: inflammatory conditions in general
Conditions
Interventions
Product Name: Lipopolysaccharide
Product Code: LPS
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: lipopolysaccharide
Current Sponsor code: LPS
Concentration un
Sponsors
Medtronic Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent to participate in this trial 2. Male subjects aged 18 to 35 years inclusive 3. Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters 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: • Use of any medication(including herbal remedies and vitamin/mineral supplements) or recreational drugs within 7 days prior to profiling day • Smoking • Use of caffeine, or alcohol or within 1 day prior to profiling day • Previous participation in a trial where LPS was administered • Surgery or trauma with significant blood loss or blood donation within 3 months prior to profiling day • Participation in another clinical trial within 3 months prior to profiling day. • History, signs or symptoms of cardiovascular disease, in particular • An implant that in the opinion of the investigator may make invasive proceedures risky for the subject due to the increased risks associated with a possible infection. • Subject has an implanted active cardiac device (ICD, IPG and/or CRT) • Implanted active neurostimulation device • Subject has internal jugular vein that cannot be accessed • History of frequent vaso-vagal collapse or of orthostatic hypotension • History of atrial or ventricular arrhythmia • Resting pulse rate =45 or =100 beats / min • Hypertension (RR systolic >160 or RR diastolic >90) • Hypotension (RR systolic 120 µmol/L • Liver function abnormality: alkaline phosphatase>230 U/L and/or ALT>90 U/L • Coagulation abnormalities: APTT or PT > 1.5 times the reference range • History of asthma • Immuno-deficiency • CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 2 weeks before profiling day • Known or suspected of not being able to comply with the trial protocol • Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the effect of transvenous vagus nerve stimulation (tVNS) on the innate immune response elicited by endotoxin administration in healthy volunteers up to 24 hours after stimulation.;Secondary Objective: • Determine effects of transvenous vagus nerve stimulation on autonomic nervous system activity up to 24 hours after stimulation • Determine effects of transvenous vagus nerve stimulation on ethylene and NO concentration in exhaled breath up to 24 hours after stimulation • Determine tolerability of acute side effects of transvenous vagus nerve stimulation • Determine ease and safety of transvenous vagus nerve stimulation delivery ;Primary end point(s): Plasma TNF-a concentration after LPS administration (Are Under Curve); comparison of subjects treated with tVNS versus sham tVNS. ;Timepoint(s) of evaluation of this end point: 0, 30, 60, 90, 120, 180, 240, 360, 480 minutes and 24 hours after endotoxin administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines (including TNF-a, IL 6, IL 1RA, IL 10) up to 24 h after LPS injection to document the immune response up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS. • Leukocyte responses to ex vivo stimulation with inflammatory stimuli and leukocyte phagocytosis capacity up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS • Endotoxemia-related clinical symptoms, hemodynamic parameters, and temperature up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS. • Endotoxemia-induced circulating leukocyte changes up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS. • Autonomic nervous system activity measured by heart rate variability up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS. • Ethylene and NO concentration in exhaled breath up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS. • Tolerability of acute side effects of tVNS • Ease of tVNS delivery ;Timepoint(s) of evaluation of this end point: at various time-points or continuous between -60 minutes and 24 hours after LPS administration. | — |
Countries
Netherlands
Contacts
Public ContactAvram Scheiner
Medtronic Inc
Outcome results
None listed