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InflammationPhase 1NoSIRSNCT01944228

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

A Phase 1 study testing Vagal Nerve Stimulation in people with Inflammation, run by Medtronic Cardiac Rhythm and Heart Failure at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 35 years, men onlyHealthy volunteers can take part
Conditions the study is for
Inflammation
What is being tested?
Vagal Nerve Stimulation
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
22 participants
Where
1 siteNetherlands
Study dates
Aug 2013to Oct 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Radboud University Nijmegen Medical Centre

    Nijmegen, 9101

Other trials in Netherlands

About this 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.

Conditions
Inflammation
Being tested
Vagal Nerve Stimulation, Sham Stimulation
Keywords
inflammation, vagus nerve stimulation, chronic heart failure, Systemic Inflammatory Response Syndrome, sepsis, auto-immune diseases
Medical subject headings
Inflammation, Systemic Inflammatory Response Syndrome, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vagal Nerve StimulationDevice

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

  • Sham StimulationDevice

    Catheter placed in the IJV without stimulation

Study groups in NCT01944228
Study groupRoleWhat they receive
Vagal Nerve StimulationExperimental30 minutes of vagal nerve stimulation using a catheter in the IJV
Receives: Device: Vagal Nerve Stimulation
Sham stimulationSham comparatorCatheter placed in the IJV without stimulation
Receives: Device: Sham Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma TNF-α concentration

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

    Measured: 24 hours

Secondary outcomes (7)

  1. Plasma concentrations of pro-inflammatory and anti-inflammatory cytokines

    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.

    Measured: up to 24 h

  2. 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

    Measured: up to 24 hrs

  3. 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.

    Measured: up to 24 hrs

  4. Endotoxemia-induced circulating leukocyte changes

    Endotoxemia-induced circulating leukocyte changes up to 24 hrs; comparison of subjects treated with tVNS versus sham tVNS.

    Measured: up to 24 hrs

  5. 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.

    Measured: up to 24 hrs

  6. Tolerability of acute side effects of tVNS

    Tolerability of acute side effects of tVNS. Subject feedback during VNS.

    Measured: Acute 30 min stimulation

  7. Ease of tVNS delivery

    Perception of delivery difficulty.

    Measured: acute interoperative

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2013 (estimated)
  2. Study startAug 2013
  3. Primary completionOct 2013
  4. Study completionOct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01944228
Sponsor's protocol ID
NoSIRS Study
Other IDs
2012-005687-97
Acronym
NoSIRS
Status last verified
Oct 2013
First submitted
12 Sep 2013
Last updated
31 Oct 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26049730

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vagal Nerve Stimulation in people with Inflammation, run by Medtronic Cardiac Rhythm and Heart Failure at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma TNF-α concentration (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01944228, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2013.

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