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

This study has been completed.
Sponsor:
Collaborator:
Radboud University
Information provided by (Responsible Party):
Medtronic Cardiac Rhythm Disease Management
ClinicalTrials.gov Identifier:
NCT01944228
First received: September 12, 2013
Last updated: October 29, 2013
Last verified: October 2013

September 12, 2013
October 29, 2013
August 2013
October 2013   (final data collection date for primary outcome measure)
Plasma TNF-α concentration [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Plasma TNF-α concentration after LPS administration (Area Under Curve); comparison of subjects treated with tVNS versus sham tVNS.
Same as current
Complete list of historical versions of study NCT01944228 on ClinicalTrials.gov Archive Site
  • Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines [ Time Frame: up to 24 h ] [ Designated as safety issue: No ]
    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.
  • Leukocyte responses to ex vivo stimulation [ Time Frame: up to 24 hrs ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 24 hrs ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 24 hrs ] [ Designated as safety issue: No ]
    Endotoxemia-induced circulating leukocyte changes up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.
  • Autonomic nervous system activity [ Time Frame: up to 24 hrs ] [ Designated as safety issue: No ]
    Autonomic nervous system activity measured by heart rate variability up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.
  • Tolerability of acute side effects of tVNS [ Time Frame: Acute 30 min stimulation ] [ Designated as safety issue: No ]
    Tolerability of acute side effects of tVNS. Subject feedback during VNS.
  • Ease of tVNS delivery [ Time Frame: acute interoperative ] [ Designated as safety issue: No ]
    Perception of delivery difficulty.
Same as current
Not Provided
Not Provided
 
Effects of Transvenous Vagus Nerve Stimulation on Immune Response: a Pilot Study
Effects of Transvenous Vagus Nerve Stimulation on Immune Response: a Pilot Study

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Inflammation
  • Device: Vagal Nerve Stimulation
    30 minutes of vagal nerve stimulation using a catheter in the IJV
  • Device: Sham Stimulation
    Catheter placed in the IJV without stimulation
  • Experimental: Vagal Nerve Stimulation
    30 minutes of vagal nerve stimulation using a catheter in the IJV
    Intervention: Device: Vagal Nerve Stimulation
  • Sham Comparator: Sham stimulation
    Catheter placed in the IJV without stimulation
    Intervention: Device: Sham Stimulation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
October 2013
October 2013   (final data collection date for primary outcome measure)

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.
Male
18 Years to 35 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01944228
NoSIRS Study, 2012-005687-97
Yes
Medtronic Cardiac Rhythm Disease Management
Medtronic Cardiac Rhythm Disease Management
Radboud University
Principal Investigator: Peter Pickkers, MD Radboud University
Medtronic Cardiac Rhythm Disease Management
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP