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

Condition(s) studied

Investigational drug(s) / intervention(s)

Active Transcutaneous Auricular Vagus Nerve Stimulation: 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.

Sham Transcutaneous Auricular Vagus Nerve Stimulation: 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.

Study 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.

Eligibility

Primary outcome measure(s)

• Proportion of Participants With a Disorder of Consciousness at Postoperative Day 90 — Postoperative day 90 (±7 days)
  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.

Trial sites (1)

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