Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06918964

TaVNS for Acute Intracerebral Hemorrhage

This study aims to evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in patients with acute intracerebral hemorrhage (ICH). The taVNS intervention will be delivered using the BS-TVNS800-1 transcutaneous electrical stimulation therapy device (KERFUN, Shanxi, China). A total of 186 patients will be randomly assigned in a 1:1 ratio to either the taVNS group or the sham-taVNS group. The primary outcome is the relative volume of perihematoma edema assessed on day 10-14 after randomization. Adverse events associated with taVNS therapy will be systematically evaluated to assess its safety profile.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Intracerebral Hemorrhage Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebral Hemorrhage Cerebrovascular Disorders Hemorrhage Inflammation Intracranial Hemorrhages Nervous System Diseases Neuroinflammatory Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with spontaneous supratentorial intracerebral hemorrhage.
  • Age between 18 and 80 years.
  • Onset within 72 hours.
  • Hematoma volume between 5 and 40 mL.
  • Glasgow Coma Scale (GCS) score greater than 8.
  • Written informed consent obtained from the patient or their legal representative.

Exclusion criteria

  • Secondary intracerebral hemorrhage (e.g., traumatic, tumor-related, vascular malformation, aneurysm, or coagulopathy-related).
  • Primary intraventricular hemorrhage.
  • Parenchymal hemorrhage that ruptures into the ventricles, with blood completely filling one lateral ventricle, the third ventricle, the fourth ventricle or more than half of both lateral ventricles.
  • Progressive neurological or other severe diseases.
  • Planned surgical treatment within 24 hours.
  • Pre-existing disability caused by previous illnesses: Modified Rankin Scale (mRS) score ≥ 3.
  • Patients with severe cardiomyopathy, heart failure, pacemaker implantation, atrial fibrillation, frequent premature beats, second-degree or higher atrioventricular block, or other severe arrhythmias.
  • Severe pulmonary disease, liver disease, renal insufficiency (glomerular filtration rate < 30 mL/min), active gastrointestinal bleeding, or malignant tumors with an expected survival of less than 3 months.
  • Patients with hyperthyroidism, hypothyroidism, syncope, epilepsy, multiple sclerosis, Parkinson's disease, multiple system atrophy, or other known disorders affecting autonomic nervous function.
  • Use of medications that interfere with autonomic function (e.g., beta-blockers, theophylline, tricyclic antidepressants, or steroids) within 7 days before screening.
  • Patients who cannot tolerate taVNS.
  • Congenital or acquired ear abnormalities preventing taVNS treatment.
  • Inability to comply with 10 days of treatment.
  • Pregnancy or within 30 days of delivery.
  • Participation in another interventional clinical trial.
  • Inability to obtain written informed consent from the participant or their legal representative.

Treatment and study plan

transcutaneous auricular vagus nerve stimulation device

Device

Place the stimulation device on the left auricle and set the stimulation parameters according to the following conditions: a. Waveform: biphase, square wave; b. Wave width: 200 μs; c. Frequency: Alternating between low frequency (4 Hz for 4 s), high frequency (40 Hz for 8 s), and a 4 s pause; d. Intensity: The maximum intensity that induces the strongest sensation the individual can tolerate without causing pain, usually 1.5-3.5 mA; e. Treatment duration: Each treatment lasted 30 minutes, twice daily (8:00, 16:00) for 10 days.

Sham device

Device

The sham taVNS group received the same parameters with a current intensity of 0.06 mA.

Primary outcomes

  1. Volume of perihematoma edema assessed by CT

    Time frame: Day 10-14 after randomization

    Relative edema volume.

Secondary outcomes

  1. Autonomic activity assessed by heart rate variability

    Time frame: Day 10-14 after randomization

    Heart rate variability (HRV) will be assessed using a 10-minute electrocardiogram (ECG) recorded with a 12-lead ECG Holter (TeleECG BI 12E, Biomedical Instruments Co., Ltd., Shenzhen). HRV indices will be analyzed in both the time domain (e.g., SDNN, RMSSD) and the frequency domain (e.g., LF, HF, LF/HF).

  2. Autonomic activity assessed by baroreflex sensitivity

    Time frame: Day 10-14 after randomization

    Baroreflex sensitivity (BRS) will be evaluated by noninvasively measuring beat-to-beat signals for 10 min using a servo-controlled plethysmograph (FMS-8A, Delica Medical Equipment Co., Ltd., Shenzhen) placed on the middle finger.

  3. National Institutes of Health stroke scale (NIHSS)

    Time frame: Day 10-14 after randomization

    NIHSS is used to assess the severity of functional impairment caused by stroke. It consists of 11 test items, with a total score ranging from 0 to 42. A higher score indicates a more severe stroke.

  4. GCS (Glasgow Coma Scale)

    Time frame: Day 10-14 after randomization

    The GCS is used to assess the level of consciousness in patients, with the total score ranging from 3 to 15. Lower scores indicate more severe impairment.

  5. MMSE (Mini-Mental State Examination)

    Time frame: Day 10-14 after randomization

    The Mini-Mental State Examination (MMSE) is a widely used cognitive screening tool designed to assess global cognitive function, including orientation, memory, attention, language, and visuospatial skills. Scores range from 0 to 30, with higher scores indicating better cognitive performance.

  6. MoCA (Montreal Cognitive Assessment)

    Time frame: Day 10-14 after randomization

    The Montreal Cognitive Assessment (MoCA) is another cognitive screening instrument optimized for detecting mild cognitive impairment (MCI) and early dementia. Scores range from 0 to 30, with higher scores indicating better cognitive performance.

  7. PHQ-9 (Patient Health Questionnaire-9)

    Time frame: Day 10-14 after randomization

    The Patient Health Questionnaire-9 (PHQ-9) is a brief, self-report tool validated for screening and monitoring depression severity. Scores range from 0 to 27, with higher scores reflecting greater symptom severity.

  8. 90-day National Institutes of Health stroke scale (NIHSS)

    Time frame: 90 ± 7 days after randomization

    NIHSS is used to assess the severity of functional impairment caused by stroke. It consists of 11 test items, with a total score ranging from 0 to 42. A higher score indicates a more severe stroke.

  9. 90-day modified Rankin Scale (mRS)

    Time frame: 90 ± 7 days after randomization

    The mRS is used to measure the degree of disability or dependence after a stroke. The scale ranges from 0 to 6 and higher scores indicate greater functional impairment.

  10. 90-day EQ-5D (EuroQol 5-Dimension Questionnaire) score

    Time frame: 90 ± 7 days after randomization

    The EQ-5D is a standardized instrument used to assess health-related quality of life.

  11. 90-day GCS (Glasgow Coma Scale)

    Time frame: 90 ± 7 days after randomization

    The GCS is used to assess the level of consciousness in patients, with the total score ranging from 3 to 15. Lower scores indicate more severe impairment.

  12. 90-day MMSE (Mini-Mental State Examination)

    Time frame: 90 ± 7 days after randomization

    The Mini-Mental State Examination (MMSE) is a widely used cognitive screening tool designed to assess global cognitive function, including orientation, memory, attention, language, and visuospatial skills. Scores range from 0 to 30, with higher scores indicating better cognitive performance.

  13. 90-day MoCA (Montreal Cognitive Assessment)

    Time frame: 90 ± 7 days after randomization

    The Montreal Cognitive Assessment (MoCA) is another cognitive screening instrument optimized for detecting mild cognitive impairment (MCI) and early dementia. Scores range from 0 to 30, with higher scores indicating better cognitive performance.

  14. 90-day PHQ-9 (Patient Health Questionnaire-9)

    Time frame: 90 ± 7 days after randomization

    The Patient Health Questionnaire-9 (PHQ-9) is a brief, self-report tool validated for screening and monitoring depression severity. Scores range from 0 to 27, with higher scores reflecting greater symptom severity.

Other outcomes

  1. Safety assessment

    Time frame: In the 10-day treatment period

    Adverse events, serious adverse events, death

  2. Perihematomal blood-brain barrier permeability

    Time frame: Day 5-7 after randomization

    Perihematomal blood-brain barrier permeability will be assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI).

  3. Evaluation of glymphatic system

    Time frame: Day 5-7 after randomization

    Impairment of the function of the glymphatic system will be assessed by diffusion kurtosis imaging analysis along the perivascular space (DKI-ALPS).

  4. Assessment of microglial activation

    Time frame: Day 7-9 after randomization

    Microglial activation will be quantified by TSPO-PET/MRI.

  5. Interleukin-1β (IL-1β) level in peripheral blood

    Time frame: Day 10-14 after randomization

    IL-1β: A pro-inflammatory cytokine (measured in pg/mL) that drives fever, neutrophil activation, and autoimmune responses. It will be detected by ELISA.

  6. Interleukin-6 (IL-6)

    Time frame: Day 10-14 after randomization

    IL-6: A pro-inflammatory cytokine (pg/mL) involved in acute-phase protein synthesis and B-cell differentiation, and implicated in infections. It will be detected by ELISA.

  7. Tumor Necrosis Factor-alpha (TNF-α)

    Time frame: Day 10-14 after randomization

    TNF-α is a pro-inflammatory cytokine (pg/mL) which can be detected via ELISA.

  8. Interleukin-4 (IL-4)

    Time frame: Day 10-14 after randomization

    IL-4 is an anti-inflammatory Th2 cytokine (pg/mL) which will be measured by ELISA.

  9. Interleukin-10 (IL-10)

    Time frame: Day 10-14 after randomization

    IL-10 is an anti-inflammatory regulator (pg/mL), which will be quantified via ELISA.

  10. Transforming Growth Factor-beta (TGF-β)

    Time frame: Day 10-14 after randomization

    TGF-β is a multifunctional cytokine (pg/mL) that is involved in regulation of cell growth, differentiation, and apoptosis. It will be detected by ELISA.

  11. Neurofilament light chain (NFL)

    Time frame: Day 10-14 after randomization

    NFL is a non-specific biological marker representing neuronal injury (measured in pg/mL). It will be measured by ELISA.

  12. Monocyte subsets

    Time frame: Day 10-14 after randomization

    Classical (CD14++CD16-) differentiate into macrophages for tissue repair, non-classical (CD14+CD16++) patrol vasculature for surveillance, measured in cells/μL by flow cytometry.

  13. CD4+ T cells

    Time frame: Day 10-14 after randomization

    Coordinate adaptive immunity (helper role, cells/μL) via cytokine secretion and immune activation, assessed by flow cytometry with surface marker staining.

  14. CD8+ T cells

    Time frame: Day 10-14 after randomization

    Mediate cytotoxicity (cells/μL), quantified using flow cytometry.

  15. NK cells

    Time frame: Day 10-14 after randomization

    Innate lymphocytes (cells/μL) detected via flow cytometry.

  16. B cells

    Time frame: Day 10-14 after randomization

    Produce antibodies for humoral immunity (measured in cells/μL), enumerated by flow cytometry (CD19/CD20 markers).

Sponsors and collaborators

Lead sponsor

Beijing Tiantan Hospital

Other

Registry information

Official study title

Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation for Acute Intracerebral Hemorrhage

Acronym: TAVANS-ICH

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Apr 9, 2025
Registry last updated
Jan 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.