The purpose of this study is to assess the effect of transvenous vagus nerve stimulation (tVNS) on the immune response. In the human endotoxemia model, intravenously administered endotoxin (lipopolysaccharide \[LPS\]) elicits a systemic immune response with release of pro-inflammatory cytokines, such as TNF α. This trial will determine if an anti-inflammatory effect can be produced by acute VNS using a minimally invasive delivery method.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
22
30 minutes of vagal nerve stimulation using a catheter in the IJV
Catheter placed in the IJV without stimulation
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands
Plasma TNF-α concentration
Plasma TNF-α concentration after LPS administration (Area Under Curve); comparison of subjects treated with tVNS versus sham tVNS.
Time frame: 24 hours
Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines
Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines (including TNF-α, 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.
Time frame: up to 24 h
Leukocyte responses to ex vivo stimulation
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
Time frame: up to 24 hrs
Endotoxemia-related clinical symptoms
Endotoxemia-related clinical symptoms, hemodynamic parameters, and temperature up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.
Time frame: up to 24 hrs
Endotoxemia-induced circulating leukocyte changes
Endotoxemia-induced circulating leukocyte changes up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.
Time frame: up to 24 hrs
Autonomic nervous system activity
Autonomic nervous system activity measured by heart rate variability up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.
Time frame: up to 24 hrs
Tolerability of acute side effects of tVNS
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Tolerability of acute side effects of tVNS. Subject feedback during VNS.
Time frame: Acute 30 min stimulation
Ease of tVNS delivery
Perception of delivery difficulty.
Time frame: acute interoperative