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

NCT01944228 | Completed Phase 1 DMC

• 2 other identifiers: NoSIRS Study2012-005687-97
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inflammation

Keywords

inflammation; vagus nerve stimulation; chronic heart failure; Systemic Inflammatory Response Syndrome; sepsis; auto-immune diseases

Outcome Measures

Primary Outcomes (1)

• Plasma TNF-α concentration

  Plasma TNF-α concentration after LPS administration (Area Under Curve); comparison of subjects treated with tVNS versus sham tVNS.

  24 hours

Secondary Outcomes (7)

• Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines

  up to 24 h

• Leukocyte responses to ex vivo stimulation

  up to 24 hrs

• Endotoxemia-related clinical symptoms

  up to 24 hrs

• Endotoxemia-induced circulating leukocyte changes

  up to 24 hrs

• Autonomic nervous system activity

  up to 24 hrs

Study Arms (2)

Vagal Nerve Stimulation

EXPERIMENTAL

30 minutes of vagal nerve stimulation using a catheter in the IJV

Device: Vagal Nerve Stimulation

Sham stimulation

SHAM COMPARATOR

Catheter placed in the IJV without stimulation

Device: Sham Stimulation

Interventions

Vagal Nerve Stimulation DEVICE

30 minutes of vagal nerve stimulation using a catheter in the IJV

Vagal Nerve Stimulation

Sham Stimulation DEVICE

Catheter placed in the IJV without stimulation

Sham stimulation

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent to participate in this trial
• Male subjects aged 18 to 35 years inclusive
• Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medtronic Cardiac Rhythm and Heart Failure: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 9101, Netherlands

Location

Related Publications (1)

• Kox M, van Eijk LT, Verhaak T, Frenzel T, Kiers HD, Gerretsen J, van der Hoeven JG, Kornet L, Scheiner A, Pickkers P. Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study. Arthritis Res Ther. 2015 Jun 7;17(1):150. doi: 10.1186/s13075-015-0667-5.

  PMID: 26049730 DERIVED

MeSH Terms

Conditions

Inflammation; Systemic Inflammatory Response Syndrome; Sepsis

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Infections

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Peter Pickkers, MD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2013
• First Posted: September 17, 2013
• Study Start: August 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 31, 2013

Record last verified: 2013-10

Locations

NL (1)