Efficacy of Transcutaneous Vagus Nerve Stimulation Paired With Tailor-Made Notched Music Therapy Versus Tailor-made Notched Music Training for Chronic Subjective Tinnitus: A Multicenter, Randomized, Double-blind, Controlled Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 388
- 主要终点
- Changes in Tinnitus Handicap Inventory (THI) scores for short-term efficacy assessment
研究概览
简要总结
This clinical study is a prospective, multicenter, randomized, controlled, double-blind clinical study. Sun Yat Sen Memorial Hospital of Sun Yat sen University was the central unit, and Nanjing First Hospital, Sun Yat Sen people's Hospital, Guanfzhou Panyu central Hospital and Zhuhai integrated traditional Chinese and Western medicine hospital were the cooperative units. In this study, 388 patients with chronic subjective tinnitus were recruited. In view of chronic subjective tinnitus, a common ear disease, the study gave the patients three months of treatment with transcutaneous vagus nerve stimulation paired with tailor-made notched music therapy or tailor-made notched music training alone. By comparing the changes of subjective scale scores related to tinnitus before and after treatment in patients receiving two different therapies, such as THI, VAS, BAI, BDI, PSQI, to evaluate the efficacy of the two therapies, so as to judge whether transcutaneous vagus nerve stimulation paired with tailor-made notched music therapy is better than tailor-made notched music training alone. In addition, the study will continue to follow up the patients after the treatment for one year to observe the difference in the long-term sustained efficacy of the two therapies. This clinical study will also evaluate the two therapies from the perspective of compliance and safety, and explore the factors that affect the efficacy of the two therapies.
详细描述
Unified rules for filling in case report forms：
- All case report forms must be completed by designated and trained researchers.
- Two data managers independently input and proofread the data in duplicate.
- The data manager will modify, confirm and enter the data according to the scales written by participant.
- The locked data file will not be changed.
- Use medical terms / concepts to record AES . The type, degree, occurrence time, duration, treatment measures and treatment process shall be recorded in detail.
Sample size estimation:
- △ THI≥ 7 points in the comparison between groups indicates that the difference in efficacy has clinical significance, the superiority margin is established.
- The pre-test results showed that △ THI = -10.2 points, SD = 10.0 points in the two groups after the treatment.
- According to unilateral inspection standard α= 0.025, inspection efficacy 1- β= 0.80, using two sample t-test to estimate the sample size, the results show that at least 155 subjects are included in each group.
- Further estimation was made according to the loss of follow-up rate of 20%. Finally, at least 194 subjects (388 persons in total) should be included in each group.
- PASS 21.0.03 (NCSs, LLC, Kaysville, Utah, USA) is adopted for the above calculation.
Plan for missing data：
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
In the whole clinical research process, the subjects and researchers participating in the efficacy and safety evaluation should be in a blind state, that is, neither of them knows the specific intervention measures given to the subjects. For participant, the treatment equipment is exactly the same between the two groups. Also, 10 seconds sham stimulation at the beginning of treatment is set in the control group for minimizing risk of participants being able to guess treatment allocation. The randomized allocation is completed by a unified randomization center. Therefore, the investigators in each center just know "A" or "B" for the allocation information of each participant. For outcomes assessors, they are only responsible for baseline and follow-up assessment during the study.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with tinnitus as the main complaint: the patients subjectively feel the sound in the ear or deep part of the head without internal or external sound stimulation, and therefore seek medical treatment
- •Chronic (≥ 6 months) and tonal tinnitus
- •Age 18-60
- •Tinnitus frequency is 125-8000 Hz
- •Hearing threshold at each frequency shall not exceed 70 dB HL
排除标准
- •Patients with conductive deafness, history of middle ear surgery, pulsatile tinnitus caused by vascular distortion and tinnitus caused by Meniere disease
- •History of head trauma, central nervous system diseases, mental diseases and drug abuse
研究组 & 干预措施
Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy
The participants receive 30 minutes / time, 4 times / day, continuous 3 months of auditory tVNS combined with TMNMT. The stimulation intensity used in each course was set to the highest level that the patient could tolerate. The participants listen to the tailor-made notched music at the same time.
干预措施: Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy (Device)
Tailor-made Notched Music Training
Similarly, 30 minutes / time, 4 times / day, continuous 3 months of TMNMT is received every day. The setting of parameters and the selection of music were the same as those in the experimental group. At the beginning of TMNMT, 10 s of sham stimulation set according to the standard of the experimental group is given.
干预措施: Tailor-made Notched Music Training (Device)
结局指标
主要结局
Changes in Tinnitus Handicap Inventory (THI) scores for short-term efficacy assessment
时间窗: From baseline to 3-month follow-up visit
Difference in the change of THI scores between two groups after 3-month treatment. The THI evaluates the severity of tinnitus in terms of emotion and function. The global scores of THI range from 0 (no disability) to 100 (serve disability).
次要结局
- Changes of Visual Analog Scale (VAS) scores in the two groups for long-term efficacy assessment(From 3-month follow-up visit to 12-month follow-up visit)
- The difference of effective connectivity based on functional magnetic resonance imaging (fMRI) between the two groups(From baseline to 12-month follow-up visit)
- Changes in scores of Visual Analog Scale (VAS) for short-term efficacy assessment(From baseline to 3-month follow-up visit)
- Changes in scores of Beck Anxiety Inventory (BAI) for short-term efficacy assessment(From baseline to 3-month follow-up visit)
- Changes of Tinnitus Handicap Inventory (THI) scores in the two groups for long-term efficacy assessment(From 3-month follow-up visit to 12-month follow-up visit)
- Changes of Beck Depression Inventory (BDI) scores in the two groups for long-term efficacy assessment(From 3-month follow-up visit to 12-month follow-up visit)
- Changes in scores of Beck Depression Inventory (BDI) for short-term efficacy assessment(From baseline to 3-month follow-up visit)
- Changes in scores of Pittsburgh sleep quality index (PSQI) for short-term efficacy assessment(From baseline to 3-month follow-up visit)
- The difference of functional connectivity based on resting state electroencephalogram (EEG) between the two groups(From baseline to 12-month follow-up visit)
- The difference of functional connectivity based on functional magnetic resonance imaging (fMRI) between the two groups(From baseline to 12-month follow-up visit)
- Changes of Beck Anxiety Inventory (BAI) scores in the two groups for long-term efficacy assessment(From 3-month follow-up visit to 12-month follow-up visit)
- Changes of Pittsburgh sleep quality index (PSQI) scores in the two groups for long-term efficacy assessment(From 3-month follow-up visit to 12-month follow-up visit)
- The effective rate of relieving chronic subjective tinnitus in the two groups(From baseline to 3-month follow-up visit)
- The difference of effective connectivity based on resting state electroencephalogram (EEG) between the two groups(From baseline to 12-month follow-up visit)