Effects of Transvenous Vagus Nerve Stimulation on Immune Response: a Pilot Study

Inflammation Clinical Trial

— NoSIRS  

Official title:

Effects of Transvenous Vagus Nerve Stimulation on Immune Response: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01944228
• Other study ID #: NoSIRS Study
• Secondary ID: 2012-005687-97
• Status: Completed
• Phase: Phase 1
• First received: September 12, 2013
• Last updated: October 29, 2013
• Start date: August 2013
• Est. completion date: October 2013

Study information

• Verified date: October 2013
• Source: Medtronic Cardiac Rhythm Disease Management
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Netherlands: Central Committee for Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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 procedures 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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Inflammation

Intervention

Device:
• Vagal Nerve Stimulation
30 minutes of vagal nerve stimulation using a catheter in the IJV
• Sham Stimulation
Catheter placed in the IJV without stimulation

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm Disease Management	Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma TNF-a concentration	Plasma TNF-a concentration after LPS administration (Area Under Curve); comparison of subjects treated with tVNS versus sham tVNS.	24 hours	No
Secondary	Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines	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.	up to 24 h	No
Secondary	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	up to 24 hrs	No
Secondary	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.	up to 24 hrs	No
Secondary	Endotoxemia-induced circulating leukocyte changes	Endotoxemia-induced circulating leukocyte changes up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.	up to 24 hrs	No
Secondary	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.	up to 24 hrs	No
Secondary	Tolerability of acute side effects of tVNS	Tolerability of acute side effects of tVNS. Subject feedback during VNS.	Acute 30 min stimulation	No
Secondary	Ease of tVNS delivery	Perception of delivery difficulty.	acute interoperative	No