Effects of Transvenous Vagus Nerve Stimulation on Immune Response: a pilot study

Phase 2

Completed

• Conditions: Condities geassocieerd met een overmatige of ongewenste immuunrespons; blood poisoning; Sepsis

• Registration Number: NL-OMON38643
• Lead Sponsor: Medtronic Inc., Cardiac Rhythm Disease Management

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 20

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

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;• 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 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 <100 or RR diastolic <50);• Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block;• Subject is diagnosed with epilepsy or history of seizures;• Renal impairment: plasma creatinine >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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Plasma TNF-a concentration after LPS administration (Area Under Curve) up to 24<br /><br>h after LPS injection; comparison of subjects treated with tVNS versus sham<br /><br>tVNS.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>We compare the following parameters in subjects treated with tVNS versus sham<br /><br>tVNS up to 24 h after LPS injection;<br /><br>- Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines<br /><br>(including TNF-a, IL 6, IL 1RA, IL 10) up to 24 h after LPS injection to<br /><br>document the innate immune response<br /><br>- Leukocyte responses to ex vivo stimulation with inflammatory stimuli and<br /><br>leukocyte phagocytosis capacity<br /><br>- Endotoxemia-related clinical symptoms, hemodynamic parameters, and temperature<br /><br>- Endotoxemia-induced circulating leukocyte changes<br /><br>- Autonomic nervous system activity measured by heart rate variability<br /><br>- Ethylene and NO concentration in exhaled breath<br /><br><br /><br>In addition we consider:<br /><br>- Tolerability of acute side effects of tVNS;<br /><br>- Ease of tVNS delivery.</p><br>