Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Training Therapy for Chronic Subjective Tinnitus

Официальное название

Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Training Therapy for Chronic Subjective Tinnitus: A Multicenter, Randomized, Controlled, Open-label Trial

Обзор

This study is a prospective, multicenter, randomized, controlled, open-label clinical trial designed to evaluate the superiority of transauricular vagus nerve microcurrent stimulation (taVNS) combined with Tailor-Made Notched Music Training (TMNMT) compared with Tinnitus Retraining Therapy (TRT) in patients with chronic subjective tinnitus. A total of 386 participants aged 18-70 years with a tinnitus duration of at least 6 months and a Tinnitus Handicap Inventory (THI) score ≥38 will be enrolled, excluding individuals with severe hearing loss, organic cranial diseases, or other contraindications. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group or the control group. The control group will receive standardized TRT, including habituation sound therapy and structured educational counseling, while the experimental group will receive TMNMT combined with taVNS (0.1 Hz pulse-train stimulation, sub-pain threshold intensity of 0.5-10 mA). Although the trial is open-label, outcome assessors and statisticians will remain blinded to group allocation. Baseline and follow-up assessments include THI, visual analog scale (VAS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), audiological evaluations, and multimodal neuroimaging using EEG and fMRI. The primary outcome is the tinnitus improvement response rate at 3 months after treatment initiation, defined as a reduction of more than 7 points in the THI score from baseline. Secondary outcomes include treatment response rates at 6 and 12 months, changes in tinnitus severity and tinnitus-related comorbid symptoms, and neuroplasticity-related changes in central neural mechanisms.

Вмешательства

• Устройство transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy
  This group receives combined transcutaneous auricular vagus nerve stimulation (taVNS) and tailor-made notched music training (TMNMT) delivered through a single, registered Class II medical device. The device synchronously administers taVNS (0.1 Hz, pulse train, 0.5-10 mA, titrated below individual pain threshold) and delivers TMNMT via integrated, phase-synchronized algorithms. The notched music is centered at the patient's tinnitus frequency with a ½-octave bandwidth. Treatment consists of 30-m
• Устройство tinnitus retraining therapy
  This group receives standard Tinnitus Retraining Therapy (TRT) using the same device platform, but without active microcurrent output. Therapy includes structured counseling and sound therapy, where broadband natural sounds are delivered at a individually set "mixing" level via the device. Daily sound exposure totals 2 hours over 3 months, supported by initial education and follow-up counseling sessions focused on habituation and cognitive restructuring.

Первичные конечные точки

• Tinnitus Improvement Response Rate [Срок оценки: Before treatment and at the end of the 3-month treatment period]

Вторичные конечные точки (11)

• Change in Self-Perceived Tinnitus Loudness assessed by Visual Analogue Scale (VAS) Score [Срок оценки: Baseline, Month 3, Month 6, Month 12]
• Change in Tinnitus Loudness Matching Threshold [Срок оценки: Baseline, Month 3, Month 6, Month 12]
• Number of Participants with Treatment-Related Adverse Events [Срок оценки: From Baseline through Month 3]
• Change in Beck Anxiety Inventory (BAI) Standardized Score [Срок оценки: Baseline, Month 3, Month 6, Month 12]
• Change in Beck Depression Inventory (BDI) Total Score [Срок оценки: Baseline, Month 3, Month 6, Month 12]
• Change in Pittsburgh Sleep Quality Index (PSQI) Global Score [Срок оценки: Baseline, Month 3, Month 6, Month 12]
• Percentage of Participants Achieving Minimal Clinically Important Difference in THI Score [Срок оценки: Month 6, Month 12]
• Change in Quantitative EEG (qEEG) Spectral and Connectivity Metrics (0.5-100 Hz) [Срок оценки: Baseline, Month 3, Month 6]
• Change in Functional MRI (fMRI) BOLD Signal and Network Connectivity [Срок оценки: Baseline, Month 3, Month 6]
• Change in Structural MRI Morphometry (Gray Matter Volume and Cortical Thickness) [Срок оценки: Baseline, Month 3, Month 6]
• Change in Diffusion MRI Metrics and Glymphatic System Activity (DTI-ALPS) [Срок оценки: Baseline, Month 3, Month 6]

Критерии участия

Критерии включения

• Patients whose primary complaint is tinnitus and who seek medical care for this reason
• Patients diagnosed with chronic tinnitus for more than 6 months
• Age between 18 and 70 years
• Tinnitus frequency within the range of 125-8000 Hz
• Hearing threshold not exceeding 70 dB HL
• Tinnitus Handicap Inventory (THI) score ≥ 38 points.

Критерии исключения

• Patients with conductive hearing loss, history of middle ear surgery, pulsatile tinnitus due to vascular malformations, or tinnitus associated with Meniere's disease
• History of head trauma, central nervous system disorders, psychiatric disorders, or substance abuse/dependence
• Patients unwilling or unable to comply with the study protocol requirements
• Patients with space-occupying lesions in the peripheral auditory pathway or central nervous system (e.g., acoustic neuroma, middle ear cholesteatoma, meningioma) as identified by imaging studies.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Гуанчжоу

Идентификаторы

NCT: NCT07469969 · SYS-5010-202601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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