Transcutaneous Auricular Vagus Nerve Stimulation for Recovery of Consciousness After Surgery for Spontaneous Intracerebral Hemorrhage

NCT07761507 | Recruiting DMC

• 1 other identifier: KY-2025-297-03
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Disorders of consciousness are common after surgery for severe spontaneous intracerebral hemorrhage and are associated with high mortality, disability, and long-term dependence. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique that may enhance arousal-network activity, modulate secondary brain injury, and promote recovery of consciousness. This multicenter, prospective, double-blind, randomized, sham-controlled trial will enroll 160 adults aged 18 to 75 years who underwent hematoma evacuation within 48 hours after spontaneous intracerebral hemorrhage and have a Glasgow Coma Scale score of 5 to 9 on postoperative day 5 while not sedated. Participants will be assigned 1:1 to active taVNS or sham stimulation for 8 hours once daily for 6 weeks. The primary outcome is the proportion of participants who remain in a disorder of consciousness (unresponsive wakefulness syndrome/vegetative state or minimally conscious state) at postoperative day 90, determined using the Coma Recovery Scale-Revised by blinded assessors. Nested mechanistic substudies will investigate how taVNS may affect recovery through multimodal assessment of structural and functional brain networks, cerebral perfusion, electrophysiology, autonomic function, and circulating or cerebrospinal-fluid biomarkers. Depending on clinical stability, site capability, sample availability, and additional consent, assessments may include computed tomography, computed tomography angiography and perfusion, structural and functional magnetic resonance imaging, diffusion imaging, arterial spin labeling, electroencephalography, blood samples, and cerebrospinal fluid obtained during clinically indicated procedures.

Conditions

Spontaneous Intracerebral Hemorrhage; Disorders of Consciousness

Keywords

Spontaneous intracerebral hemorrhage; Postoperative disorder of consciousness; Transcutaneous auricular vagus nerve stimulation; Recovery of consciousness; Coma Recovery Scale-Revised

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With a Disorder of Consciousness at Postoperative Day 90

  The proportion of participants classified by the Coma Recovery Scale-Revised (CRS-R) as being in unresponsive wakefulness syndrome/vegetative state (UWS/VS) or a minimally conscious state (MCS- or MCS+). Participants classified as having emerged from the minimally conscious state (eMCS) or as conscious are considered not to have a disorder of consciousness. The day-90 assessment is performed by independent assessors blinded to treatment assignment. A lower proportion indicates a better outcome.

  Postoperative day 90 (±7 days)

Secondary Outcomes (13)

• Clinical Consciousness Improvement Response at Postoperative Day 90

  Baseline on postoperative day 5 (±1 day) to postoperative day 90 (±7 days)

• Clinical Consciousness Improvement Response at Postoperative Day 28

  Baseline on postoperative day 5 (±1 day) to postoperative day 28 (±3 days)

• Ordinal Distribution of Consciousness States at Postoperative Day 90

  Postoperative day 90 (±7 days)

• Change From Baseline in Coma Recovery Scale-Revised Total Score at Postoperative Day 28

  Baseline on postoperative day 5 (±1 day) to postoperative day 28 (±3 days)

• Change From Baseline in Coma Recovery Scale-Revised Total Score at Postoperative Day 90

  Baseline on postoperative day 5 (±1 day) to postoperative day 90 (±7 days)

Study Arms (2)

Active taVNS

EXPERIMENTAL

Participants receive active transcutaneous auricular vagus nerve stimulation at the left ear for 8 hours once daily for 6 weeks, in addition to standard postoperative and rehabilitation care.

Device: Active Transcutaneous Auricular Vagus Nerve Stimulation

Sham taVNS

SHAM COMPARATOR

Participants wear the same taVNS device with the electrode placed at the same left-ear location for 8 hours once daily for 6 weeks, but no electrical current is delivered. Standard postoperative and rehabilitation care is otherwise provided.

Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation

Interventions

Active Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

Active taVNS is delivered to the left ear at a frequency of 25 Hz, a pulse width of 500 microseconds, and a current intensity of 0.8-1.5 mA. Stimulation alternates between 30 seconds on and 30 seconds off for a total wearing period of 8 hours once daily. Treatment begins after randomization on postoperative day 5 (±1 day) and continues for 6 weeks.

Active taVNS

Sham Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

The sham device is worn at the same left-ear location and for the same schedule as active taVNS (8 hours once daily for 6 weeks), but no electrical current is delivered.

Sham taVNS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Spontaneous intracerebral hemorrhage.
• Age 18 to 75 years.
• Surgical intervention performed within 48 hours after symptom onset.
• Glasgow Coma Scale score of 5 to 9 on postoperative day 5 while the participant is not sedated; for intubated participants, the verbal component is scored as 1T.
• Surgical hematoma evacuation by craniotomy, endoscopic evacuation, or minimally invasive aspiration/fragmentation.
• Written informed consent provided by the participant's legally authorized representative.

You may not qualify if:

• Intracranial hemorrhage caused by a confirmed intracranial aneurysm, cerebral vascular malformation, intracranial tumor, arterial thrombosis, or venous thrombosis.
• Injury to critical brain structures affecting consciousness, including brainstem hemorrhage or thalamic hemorrhage greater than 20 mL.
• Isolated intraventricular hemorrhage.
• Severe cardiomyopathy, heart failure, atrial fibrillation, frequent premature beats, second-degree or higher atrioventricular block, or another severe cardiac arrhythmia.
• Unstable postoperative vital signs, defined as systolic blood pressure below 90 mm Hg or heart rate below 50 beats per minute.
• New cerebral infarction or recurrent intracranial hemorrhage between surgery and randomization.
• Acute myocardial ischemia or myocardial infarction between surgery and randomization.
• Previous vagus nerve electrical stimulation, previous cervical vagotomy, concurrent use of another stimulation device, or presence of an implanted electronic medical device, including a muscle stimulator, cardiac pacemaker, hearing aid, or any other implanted electronic device.
• Skin breakdown, infection, erythema, or another condition at the electrode-placement site that makes taVNS unsuitable.
• Pregnant, peripartum, or postpartum women.
• Current participation in another clinical trial.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Beijing Friendship Hospital: collaborator
• First Affiliated Hospital of Fujian Medical University: collaborator
• Liaocheng People's Hospital: collaborator

Study Sites (1)

Capital Medical University Affliated Beijing Tiantan Hospital, Beijing, Beijing

Beijing, China

RECRUITING

MeSH Terms

Conditions

Consciousness Disorders

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Qingyuan Liu, M.D.

CONTACT

+86-13260457220; 13260457220@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and the independent outcome assessors are blinded to treatment assignment. Active and sham devices are applied at the same left-ear location for the same duration. The sham device delivers no electrical current. Group allocation is concealed from the outcome-assessment team until the database is locked, except when emergency unblinding is required.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Cerebrovascular Neurosurgery

Model Details: Participants are assigned in a 1:1 ratio to active taVNS or sham stimulation and remain in the assigned group throughout the 6-week treatment period.

Study Record Dates

• First Submitted: August 2, 2026
• First Posted: August 12, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 12, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)