Non-Invasively Re-Training the Tinnitus Brain Using Bimodal Electrical-Sound Stimulation (NITESGON-ADT): Protocol for a Prospective, Double-Blind, Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Tinnitus Loudness (Visual Analogue Scale, VAS 0-100)
研究概览
简要总结
This study tests whether pairing non-invasive stimulation of the greater occipital nerve (NITESGON) with an attentionally demanding auditory frequency discrimination training task reduces tinnitus loudness and tinnitus-related distress. One hundred adults with chronic tonal tinnitus will be randomised to one of four groups in a 2×2 factorial design: real versus sham NITESGON and active versus passive listening during auditory stimulation. Participants complete eight sessions across four weeks, with outcomes assessed at baseline, end of treatment, 28 days post-treatment, and 6 months post-treatment.
详细描述
This is a single-centre, prospective, double-blind, placebo-controlled, 2×2 factorial randomised controlled trial conducted at Trinity College Dublin. The intervention combines transcutaneous electrical stimulation targeting the greater occipital nerve (NITESGON) with auditory stimulation delivered during a structured training paradigm. The two between-subjects factors are stimulation condition (real NITESGON vs sham NITESGON) and listening condition (active listening: auditory frequency discrimination training vs passive listening: visual distractor task while auditory stimuli are presented). One hundred adults with chronic tonal tinnitus will be randomised 1:1:1:1 to one of four arms. Participants complete eight sessions (two per week for four weeks). Primary outcomes-tinnitus loudness (VAS 0-100), tinnitus-related functional impact (TFI 0-100), and tinnitus handicap (THI 0-100)-and secondary outcomes are assessed at baseline (T0), end of treatment (T1), 28 days after treatment completion (T2), and 6 months after treatment completion (T3). Secondary outcomes include tinnitus psychoacoustics, extended high-frequency audiometry, speech-in-noise performance, EEG (resting-state and auditory oddball), autonomic/biomarker measures (pupillometry, heart rate, saliva), patient global impression of change, quality of life, and safety/blinding assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Participants are blinded to stimulation condition (real vs sham NITESGON). Outcome assessors and data analysts are blinded to group allocation. The investigator operating the stimulation device does not take part in outcome assessments and follows coded procedures to deliver real or sham stimulation.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-80 years
- •Continuous subjective tinnitus for >3 months and ≤5 years
- •Predominantly tonal tinnitus (unilateral or bilateral)
- •Screening THI score 28-76
- •Minimum Masking Level (MML) 20-80 dB HL
- •No prior tinnitus neuromodulation treatment
- •Able to comply with eight sessions over four weeks and follow-up assessments
排除标准
- •Objective tinnitus or predominantly somatic tinnitus
- •Pulsatile tinnitus
- •Evidence of conductive hearing loss (abnormal otoscopy or tympanometry)
- •Pure-tone audiometry exclusions: >40 dB HL at any frequency 250 Hz-1 kHz OR >80 dB HL at any frequency 2-8 kHz in either ear
- •Hearing aid use initiated within the past 90 days
- •Active implantable medical device (e.g., pacemaker, DBS, cochlear implant)
- •LDL <30 dB SL at 500 Hz in either ear
- •Diagnosis of temporomandibular joint disorder or occipital neuralgia
- •Severe anxiety (STAI >120/160)
- •Cognitive impairment (MMSE <25)
- •Severe depressive symptoms (BDI ≥30)
- •Diagnosis of Menière's disease
- •Current pregnancy
- •Involvement in medicolegal cases
- •History of auditory hallucinations
- •Current prescription of central nervous system drugs likely to alter neuromodulatory function (e.g., noradrenergic, dopaminergic, serotonergic, benzodiazepine, cholinergic, or other psychoactive medications)
- •Currently enrolled in another interventional study
研究组 & 干预措施
Real Stimulation + Active Listening (ADT)
Real stimulation delivered during active auditory frequency discrimination training.
干预措施: Real NITESGON (Device)
Real Stimulation + Active Listening (ADT)
Real stimulation delivered during active auditory frequency discrimination training.
干预措施: Active Listening (Behavioral)
Real Stimulation + Passive Listening
Real stimulation delivered while participants perform a visual distractor task and are instructed to ignore auditory stimuli.
干预措施: Real NITESGON (Device)
Real Stimulation + Passive Listening
Real stimulation delivered while participants perform a visual distractor task and are instructed to ignore auditory stimuli.
干预措施: Passive Listening (Control) (Behavioral)
Sham Stimulation + Active Listening (ADT)
Sham stimulation delivered during active auditory frequency discrimination training.
干预措施: Sham NITESGON (Device)
Sham Stimulation + Active Listening (ADT)
Sham stimulation delivered during active auditory frequency discrimination training.
干预措施: Active Listening (Behavioral)
Sham Stimulation + Passive Listening
Sham stimulation delivered while participants perform a visual distractor task and are instructed to ignore auditory stimuli.
干预措施: Sham NITESGON (Device)
Sham Stimulation + Passive Listening
Sham stimulation delivered while participants perform a visual distractor task and are instructed to ignore auditory stimuli.
干预措施: Passive Listening (Control) (Behavioral)
结局指标
主要结局
Tinnitus Loudness (Visual Analogue Scale, VAS 0-100)
时间窗: Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.
0-100 mm VAS anchored from "not audible" to "extremely loud"; higher scores indicate greater perceived tinnitus loudness.
Tinnitus Functional Index (TFI, 0-100)
时间窗: Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.
25-item self-report measure of tinnitus-related functional impact; total score 0-100, higher scores indicate greater impairment.
Tinnitus Handicap Inventory (THI, 0-100)
时间窗: Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.
25-item measure of tinnitus-related handicap; total score 0-100, higher scores indicate greater handicap.
次要结局
- Audiometry (Extended High-Frequency Thresholds up to 13 kHz)(Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Speech-in-Noise Performance (e.g., QuickSIN)(Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Patient Global Impression of Change (PGIC)(End of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Quality of Life (World Health Organization Quality of Life-BREF questionnaire)(Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Adverse Events (Stimulation Side-Effects Questionnaire)(Up to 4 weeks (Sessions 1-8))
- Tinnitus Pitch Matching(Baseline, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Tinnitus Loudness Matching and Discomfort Levels(Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Minimum Masking Level (MML)(Baseline visit, end of treatment at 4 weeks, 28 days post-treatment, and 6 months post-treatment.)
- Resting-State EEG Spectral Power (Eyes Closed)(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
- Resting-State EEG Functional Connectivity (Eyes Closed)(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
- Auditory Oddball Task-Evoked Response Amplitude(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
- Auditory Oddball Task-Evoked Response Latency(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
- Pupillometry(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
- Heart Rate(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
- Saliva Biomarkers(Baseline visit, end of treatment (4 weeks), 28 days post-treatment, and 6 months post-treatment.)
研究者
Sven Vanneste
Professor
University of Dublin, Trinity College