SepsisSNV-SepsisNCT04774705
Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.
A study testing SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) in people with Sepsis and Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock
- What is being tested?
- SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 29 Mar 2021to 29 Mar 2025
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Informed consent signed by patient or family member/trusted support person
- In an emergency situation, in the absence of family members/trusted family/trusted support person
Who cannot join
- Patient under guardianship or curatorship
- 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,
Show all 10Show fewer
- No affiliation to a social security scheme.
- Patient with cochlear implant
- Patient with heart disease
- Patient with asthma
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Raymond Poincaré Hospital
Garches
Eric AZABOU, +331 47 10 79 40
About this study
Official title: 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.
- Conditions
- Sepsis, Septic Shock
- Being tested
- SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ), Placebo group
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )Other
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 groupOther
For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.
| Study group | Role | What they receive |
|---|---|---|
| SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) | Experimental | Not described Receives: Other: SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) |
| Control group | Placebo comparator | For the SNV placebo group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule. Receives: Other: Placebo group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Overall death
Measured: at day 90
Secondary outcomes (52)
Cumulative incidence of delirium and its duration
Measured: up to day 90
Cumulative incidence of mechanical ventilation and its duration
Measured: up to day 90
Proportion of patients having been the subject of a decision to limit or withdraw care
Measured: at day 90
Duration of use of vasopressors
Measured: at day 90
Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6
Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function
Measured: at day 90
Length of stay in intensive care and hospitalization in all patients and in survivors
Measured: at day 90
Measurements of changes in C-reactive protein (CRP)
Measured: at inclusion
Measurements of changes in C-reactive protein (CRP)
Measured: at day 7
Measurements of changes in C-reactive protein (CRP)
Measured: at day 14
Measurements of changes in C-reactive protein (CRP)
Measured: at day 21
Measurements of changes in C-reactive protein (CRP)
Measured: at day 28
Measurements of changes in C-reactive protein (CRP)
Measured: at day 90
Measurements of changes in fibrinogen level
Measured: at inclusion
Measurements of changes in fibrinogen level
Measured: at day 7
Measurements of changes in fibrinogen level
Measured: at day 14
Measurements of changes in fibrinogen level
Measured: at day 21
Measurements of changes in fibrinogen level
Measured: at day 28
Measurements of changes in fibrinogen level
Measured: at day 90
Measurements of changes in interleukin-6 (IL-6)
Measured: at inclusion
Measurements of changes in interleukin-6 (IL-6)
Measured: at day 7
Measurements of changes in interleukin-6 (IL-6)
Measured: at day 14
Measurements of changes in interleukin-6 (IL-6)
Measured: at day 21
Measurements of changes in interleukin-6 (IL-6)
Measured: at day 28
Measurements of changes in interleukin-6 (IL-6)
Measured: at day 90
Measurements of changes in interleukin-1β (IL-1β)
Measured: at inclusion
Measurements of changes in interleukin-1β (IL-1β)
Measured: at day 7
Measurements of changes in interleukin-1β (IL-1β)
Measured: at day 14
Measurements of changes in interleukin-1β (IL-1β)
Measured: at day 21
Measurements of changes in interleukin-1β (IL-1β)
Measured: at day 28
Measurements of changes in interleukin-1β (IL-1β)
Measured: at day 90
Measurements of changes in tumor necrosis factor α (TNF-α)
Measured: at inclusion
Measurements of changes in tumor necrosis factor α (TNF-α)
Measured: at day 7
Measurements of changes in tumor necrosis factor α (TNF-α)
Measured: at day 14
Measurements of changes in tumor necrosis factor α (TNF-α)
Measured: at day 21
Measurements of changes in tumor necrosis factor α (TNF-α)
Measured: at day 28
Measurements of changes in tumor necrosis factor α (TNF-α)
Measured: at day 90
Measurements of changes in the calcium binding protein B S100B (S100B)
Measured: at inclusion
Measurements of changes in the calcium binding protein B S100B (S100B)
Measured: at day 7
Measurements of changes in the calcium binding protein B S100B (S100B)
Measured: at day 14
Measurements of changes in the calcium binding protein B S100B (S100B)
Measured: at day 21
Measurements of changes in the calcium binding protein B S100B (S100B)
Measured: at day 28
Measurements of changes in the calcium binding protein B S100B (S100B)
Measured: at day 90
Measurements of changes in the arterial lactate level
Measured: at inclusion
Measurements of changes in the arterial lactate level
Measured: at day 7
Measurements of changes in the arterial lactate level
Measured: at day 14
Measurements of changes in the arterial lactate level
Measured: at day 21
Measurements of changes in the arterial lactate level
Measured: at day 28
Measurements of changes in the arterial lactate level
Measured: at day 90
Characteristics of the EEG
Measured: at inclusion
Characteristics of the EEG
Measured: at day 7
Mortality rate
Overall death
Measured: at day 28
Neurological fate of patients
Neurological fate of patients will evaluated using Glasgow Outcome Scale (GOS)
Measured: at day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2021
- Study start29 Mar 2021
- Primary completion29 Mar 2025 (estimated)
- Study completion29 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04774705
- Sponsor's protocol ID
- D20170804
- Acronym
- SNV-Sepsis
- Status last verified
- Jul 2024
- First submitted
- 24 Feb 2021
- Last updated
- 17 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Dec 1;36(12):2473-2484. doi: 10.1681/ASN.0000000813. Epub 2025 Jul 7.
PubMed 40622772
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Pilot Study Evaluating the Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.
- ClinicalTrials.gov ID
- NCT04774705
- Acronym / sponsor ID
- SNV-Sepsis / D20170804
- Conditions
- Sepsis, Septic Shock
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 29 Mar 2025 (estimated)
- Study completion
- 29 Mar 2025 (estimated)
- First posted
- 1 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) | Experimental | Other: SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) |
| Control group | Placebo comparator | Other: Placebo groupFor the SNV placebo group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
- Informed consent signed by patient or family member/trusted support person
- In an emergency situation, in the absence of family members/trusted family/trusted support person
Key exclusion criteria (10 listed)
- Patient under guardianship or curatorship
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) |
| Placebo groupFor the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule. | Other | Control group |
Primary outcome
Mortality
Time frame: at day 90
Overall death
52 secondary outcomes
Cumulative incidence of delirium and its duration
Time frame: up to day 90
Cumulative incidence of mechanical ventilation and its duration
Time frame: up to day 90
Proportion of patients having been the subject of a decision to limit or withdraw care
Time frame: at day 90
Duration of use of vasopressors
Time frame: at day 90
Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6
Time frame: at day 90
Length of stay in intensive care and hospitalization in all patients and in survivors
Time frame: at day 90
Measurements of changes in C-reactive protein (CRP)
Time frame: at inclusion
Measurements of changes in C-reactive protein (CRP)
Time frame: at day 7
Measurements of changes in C-reactive protein (CRP)
Time frame: at day 14
Measurements of changes in C-reactive protein (CRP)
Time frame: at day 21
Measurements of changes in C-reactive protein (CRP)
Time frame: at day 28
Measurements of changes in C-reactive protein (CRP)
Time frame: at day 90
Measurements of changes in fibrinogen level
Time frame: at inclusion
Measurements of changes in fibrinogen level
Time frame: at day 7
Measurements of changes in fibrinogen level
Time frame: at day 14
Measurements of changes in fibrinogen level
Time frame: at day 21
Measurements of changes in fibrinogen level
Time frame: at day 28
Measurements of changes in fibrinogen level
Time frame: at day 90
Measurements of changes in interleukin-6 (IL-6)
Time frame: at inclusion
Measurements of changes in interleukin-6 (IL-6)
Time frame: at day 7
Measurements of changes in interleukin-6 (IL-6)
Time frame: at day 14
Measurements of changes in interleukin-6 (IL-6)
Time frame: at day 21
Measurements of changes in interleukin-6 (IL-6)
Time frame: at day 28
Measurements of changes in interleukin-6 (IL-6)
Time frame: at day 90
Measurements of changes in interleukin-1β (IL-1β)
Time frame: at inclusion
Measurements of changes in interleukin-1β (IL-1β)
Time frame: at day 7
Measurements of changes in interleukin-1β (IL-1β)
Time frame: at day 14
Measurements of changes in interleukin-1β (IL-1β)
Time frame: at day 21
Measurements of changes in interleukin-1β (IL-1β)
Time frame: at day 28
Measurements of changes in interleukin-1β (IL-1β)
Time frame: at day 90
Measurements of changes in tumor necrosis factor α (TNF-α)
Time frame: at inclusion
Measurements of changes in tumor necrosis factor α (TNF-α)
Time frame: at day 7
Measurements of changes in tumor necrosis factor α (TNF-α)
Time frame: at day 14
Measurements of changes in tumor necrosis factor α (TNF-α)
Time frame: at day 21
Measurements of changes in tumor necrosis factor α (TNF-α)
Time frame: at day 28
Measurements of changes in tumor necrosis factor α (TNF-α)
Time frame: at day 90
Measurements of changes in the calcium binding protein B S100B (S100B)
Time frame: at inclusion
Measurements of changes in the calcium binding protein B S100B (S100B)
Time frame: at day 7
Measurements of changes in the calcium binding protein B S100B (S100B)
Time frame: at day 14
Measurements of changes in the calcium binding protein B S100B (S100B)
Time frame: at day 21
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2024.
- Derived from this study: PubMed 40622772Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Dec 1;36(12):2473-2484. doi: 10.1681/ASN.0000000813. Epub 2025 Jul 7.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve ) in people with Sepsis and Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 17 Jul 2024. 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 France. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eric AZABOU (+331 47 10 79 40, eric.azabou@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: at day 90). 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 NCT04774705, 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 17 Jul 2024.