The Role of Transcutaneous Vagus Nerve Stimulation in Treatment of Acute Brain Injury

NCT07384845 | Not Yet Recruiting

• 1 other identifier: 02/013AG
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Acute brain injury is a major global health problem associated with high mortality and morbidity, limited therapeutic options, prolonged hospital stays, and long-term disability that significantly impairs quality of life and increases healthcare costs. Noninvasive transcutaneous VNS developed as a safer approach for treating cerebral edema, epileptic seizures, and blood-brain barrier disruption, for facilitating the recovery of motoric and cognitive functions, and for immunomodulation. Transcutaneous VNS improves cerebral perfusion pressure and tissue oxygenation, supports reperfusion of the penumbral zone, and reduces neuronal hyperexcitability, thereby suppressing seizures.It may exert anti-inflammatory effects by reducing microglial cytokine and chemokine production. Additionally, vagal stimulation promotes acetylcholine-mediated suppression of pro-inflammatory cytokines, including TNF, IL-1β, IL-6, and IL-18. Another anti-inflammatory mechanism involves ghrelin, a peptide hormone whose serum levels increase under vagal stimulation. Elevated ghrelin reduces TNF-α and other pro-inflammatory cytokines and may limit intracerebral hemorrhage by inhibiting the NLRP3 inflammasome and activating the Nrf2/ARE signaling pathway. Biomarkers such as S100 protein and neuron-specific enolase (NSE) are valuable indicators of brain tissue damage and clinical outcomes; tVNS may reduce their levels and support non-invasive monitoring of disease progression. The technique is considered safe in patients . To date, tVNS has not been evaluated in clinical trials in Croatia, nor reported in case studies or cohort analyses. Study outcomes will be correlated with patients' clinical status, duration and course of hospitalization, complication rates, and overall treatment outcomes.

Conditions

Acute Brain Injury; Transcutaneous Vagus Nerve Stimulation; Neuromodulation; Immunomodulation

Outcome Measures

Primary Outcomes (3)

• Biomarkers of traumatic brain injury (S100B, neuron-specific enolase, GFAP) and ghrelin

  To measure and analyze the concentrations of biomarkers of traumatic brain injury (S100B, neuron-specific enolase \[NSE\], GFAP) as well as the peptide hormone ghrelin, in serum and cerebrospinal fluid within 24 hours of admission to the intensive care unit (ICU), and again after 7 days.

  7 days

• Cytokine concentrations in serum and cerebrospinal fluid (IL-1β, IL-6, TNF-α, IL-10)

  To measure and analyze concentration of cytokines in serum and cerebrospinal fluid (IL-1β, IL-6, TNF-α, IL-10) within 24 hours of admission to the intensive care unit (ICU), and again after 7 days

  7 days

• CT angiography in patients with aneurysmatic SAH

  Radiologically monitor the presence, development, and severity of vasospasm in patients with aSAH using CT angiography on two occasions: within 24 hours of the ruptured aneurysm closure, and on the 7th day after aneurysm closure

  7 days

Study Arms (2)

Acute brain injury patients with tVNS stimulation

ACTIVE COMPARATOR

tVNS will be applied on left tragus, followed by stimulation with 20 Hz twice daily. Biomarkers of traumatic brain injury (S100B, neuron-specific enolase, GFAP), ghrelin and cytokine concentrations in serum and cerebrospinal fluid (IL-1β, IL-6, TNF-α, IL-10) will be measured on two occasions. CT angiography on the first and seventh day for patients with SAH.

Device: transcutaneous vagus nerve stimulation (tVNS)

Acute brain injury patients with sham

SHAM COMPARATOR

tVNS VNS will be applied on left tragus, but without stimulation in the same time frame as in the first group. Biomarkers of traumatic brain injury (S100B, neuron-specific enolase, GFAP), ghrelin and cytokine concentrations in serum and cerebrospinal fluid (IL-1β, IL-6, TNF-α, IL-10) will be measured on two occasions. CT angiography on the first and seventh day for patients with SAH.

Device: Sham (No Treatment)

Interventions

transcutaneous vagus nerve stimulation (tVNS) DEVICE

application of tVNS in patients with acute brain injury

Acute brain injury patients with tVNS stimulation

Sham (No Treatment) DEVICE

TVNS will be placed in the same manner as in the first group, but without vagal stimulation

Acute brain injury patients with sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 18 years of age with a diagnosis of traumatic brain injury or acute subarachnoid hemorrhage due to rupture of an intracranial aneurysm, confirmed by brain CT or MRI.

You may not qualify if:

• Patients under 18 years of age; patients with autoimmune diseases or malignant diseases; pregnant women; and patients for whom informed consent to participate in the study is not obtained.

Sponsors & Collaborators

• Clinical Hospital Centre Zagreb: lead

Study Sites (1)

UHCZagreb

Zagreb, 10000, Croatia

Location

MeSH Terms

Conditions

Brain Injuries

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Dinko Tonković, Prof, MD PhD

  Clinical Hospital Centre Zagreb

  PRINCIPAL INVESTIGATOR

• Martina Miklić Bublić, MD PhD

  Clinical Hospital Centre Zagreb

  PRINCIPAL INVESTIGATOR

• Dunja Rogić, Prof, MD PhD

  Clinical Hospital Centre Zagreb

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dinko Tonković, MD, PhD

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 3, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)