Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care. (SNV-Sepsis)

Randomized Pilot Study Evaluating the Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.

Sepsis is one of the leading causes of death in intensive care. About 50% of patients with septic shock die after 1 year; and 50% of survivors suffer from cognitive decline. The pathophysiological mechanisms of serious complications of sepsis are now well known. In fact, the systemic inflammation related to sepsis amplifies the release of pro-inflammatory cytokines and neurotoxic mediators, hence an increase in deleterious phenomena such as oxidative stress, mitochondrial dysfunction, endothelial activation, disruption of the blood-brain barrier, neuroinflammation (astrocytic and microglial activation) leading to multi-organ failure which compromises the patient's vital and functional prognosis. Although there has been progress in the understanding of its pathophysiology, the management of sepsis and septic shock in intensive care relies mainly on anti-infective treatments and the restoration of cardiovascular and respiratory functions. There is virtually no adjuvant therapy for the management of sepsis, apart from a few hormonal therapies such as insulin to maintain blood glucose levels below 180 mg / dL and low doses of corticosteroids and vasopressin. There is therefore a pressing need to develop innovative treatments targeting inflammatory and immunological processes in order to reduce the complications of sepsis and improve patient prognosis. Some recent work has shown that electrical vagus nerve stimulation (SNV), a technique used for the treatment of drug-resistant epilepsy, can modulate inflammatory and immune responses and control inflammation syndrome in animal models of sepsis, arthritis and rheumatism in humans. In this pilot study the investigators plan to evaluate the efficacy of transcutaneous (non-invasive) SNV as an adjuvant treatment in patients with sepsis in intensive care.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Other: SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ); Other: Placebo group

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric AZABOU; Phone Number: +331 47 10 79 40; Email: eric.azabou@aphp.fr

Study Locations

• France
  • Garches, France
    • Recruiting
    • Raymond Poincaré Hospital
    • Contact: Eric AZABOU; Phone Number: +331 47 10 79 40

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age> 18 years old
• Adult man or woman, hospitalized in intensive care, presenting with sepsis for at least 24 hours according to the diagnostic criteria (Singer et al., 2016).

Exclusion Criteria:

• Patient under guardianship,
• Patient in a severe state of agitation.
• Patient in a state of brain death or active limitation of treatment.
• Multiple trauma patient, with multiple fractures of the skull.
• Refusal to participate in the study or to sign the informed consent by the patient or his loved one,
• Pregnant or breastfeeding woman,
• No affiliation to a social security scheme.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )	Other: SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ); A transcutaneous stimulator of the atrial branch of the vagus nerve of the TENS eco Plus type (Schwa-medico) will be used. SNV stimulation will be applied in the concha of the left ear to the subcutaneous area of the atrial branch of the vagus nerve in the left ear (cymba conchae) for each patient, at an intensity of 2 mA, 30 minutes per day for 5 consecutive days, from the day of inclusion / randomization.
Placebo Comparator: Control group; For the SNV placebo group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.	Other: Placebo group; For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Overall death	at day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of delirium and its duration		up to day 90
Cumulative incidence of mechanical ventilation and its duration		up to day 90
Proportion of patients having been the subject of a decision to limit or withdraw care		at day 90
Duration of use of vasopressors		at day 90
Number of days alive with a SOFA score <6		at day 90
Length of stay in intensive care and hospitalization in all patients and in survivors		at day 90
Measurements of changes in C-reactive protein (CRP)		at inclusion
Measurements of changes in C-reactive protein (CRP)		at day 7
Measurements of changes in C-reactive protein (CRP)		at day 14
Measurements of changes in C-reactive protein (CRP)		at day 21
Measurements of changes in C-reactive protein (CRP)		at day 28
Measurements of changes in C-reactive protein (CRP)		at day 90
Measurements of changes in fibrinogen level		at inclusion
Measurements of changes in fibrinogen level		at day 7
Measurements of changes in fibrinogen level		at day 14
Measurements of changes in fibrinogen level		at day 21
Measurements of changes in fibrinogen level		at day 28
Measurements of changes in fibrinogen level		at day 90
Measurements of changes in interleukin-6 (IL-6)		at inclusion
Measurements of changes in interleukin-6 (IL-6)		at day 7
Measurements of changes in interleukin-6 (IL-6)		at day 14
Measurements of changes in interleukin-6 (IL-6)		at day 21
Measurements of changes in interleukin-6 (IL-6)		at day 28
Measurements of changes in interleukin-6 (IL-6)		at day 90
Measurements of changes in interleukin-1β (IL-1β)		at inclusion
Measurements of changes in interleukin-1β (IL-1β)		at day 7
Measurements of changes in interleukin-1β (IL-1β)		at day 14
Measurements of changes in interleukin-1β (IL-1β)		at day 21
Measurements of changes in interleukin-1β (IL-1β)		at day 28
Measurements of changes in interleukin-1β (IL-1β)		at day 90
Measurements of changes in tumor necrosis factor α (TNF-α)		at inclusion
Measurements of changes in tumor necrosis factor α (TNF-α)		at day 7
Measurements of changes in tumor necrosis factor α (TNF-α)		at day 14
Measurements of changes in tumor necrosis factor α (TNF-α)		at day 21
Measurements of changes in tumor necrosis factor α (TNF-α)		at day 28
Measurements of changes in tumor necrosis factor α (TNF-α)		at day 90
Measurements of changes in the calcium binding protein B S100B (S100B)		at inclusion
Measurements of changes in the calcium binding protein B S100B (S100B)		at day 7
Measurements of changes in the calcium binding protein B S100B (S100B)		at day 14
Measurements of changes in the calcium binding protein B S100B (S100B)		at day 21
Measurements of changes in the calcium binding protein B S100B (S100B)		at day 28
Measurements of changes in the calcium binding protein B S100B (S100B)		at day 90
Measurements of changes in the arterial lactate level		at inclusion
Measurements of changes in the arterial lactate level		at day 7
Measurements of changes in the arterial lactate level		at day 14
Measurements of changes in the arterial lactate level		at day 21
Measurements of changes in the arterial lactate level		at day 28
Measurements of changes in the arterial lactate level		at day 90
Characteristics of the EEG		at inclusion
Characteristics of the EEG		at day 7
Mortality rate	Overall death	at day 28
Neurological fate of patients	Neurological fate of patients will evaluated using Glasgow Outcome Scale - GOS	at day 90

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Anticipated): March 29, 2023
• Study Completion (Anticipated): March 29, 2023

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: D20170804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No