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
  Purpose

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.


Condition Intervention Phase
Inflammation
Device: Vagal Nerve Stimulation
Device: Sham Stimulation
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Transvenous Vagus Nerve Stimulation on Immune Response: a Pilot Study

Further study details as provided by Medtronic Cardiac Rhythm Disease Management:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 22
Study Start Date: August 2013
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vagal Nerve Stimulation
30 minutes of vagal nerve stimulation using a catheter in the IJV
Device: Vagal Nerve Stimulation
30 minutes of vagal nerve stimulation using a catheter in the IJV
Sham Comparator: Sham stimulation
Catheter placed in the IJV without stimulation
Device: Sham Stimulation
Catheter placed in the IJV without stimulation

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01944228

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 9101
Sponsors and Collaborators
Medtronic Cardiac Rhythm Disease Management
Radboud University
Investigators
Principal Investigator: Peter Pickkers, MD Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: Medtronic Cardiac Rhythm Disease Management
ClinicalTrials.gov Identifier: NCT01944228     History of Changes
Other Study ID Numbers: NoSIRS Study, 2012-005687-97
Study First Received: September 12, 2013
Last Updated: October 29, 2013
Health Authority: The Netherlands: Central Committee for Research Involving Human Subjects (CCMO)

Keywords provided by Medtronic Cardiac Rhythm Disease Management:
inflammation
vagus nerve stimulation
chronic heart failure
Systemic Inflammatory Response Syndrome
sepsis
auto-immune diseases

Additional relevant MeSH terms:
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on August 21, 2014