Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor.
Consulting for Statistics, Computing and Analytics Research, University of Michigan, Ann Arbor.
JAMA Netw Open. 2023 Jun 1;6(6):e2315914. doi: 10.1001/jamanetworkopen.2023.15914.
IMPORTANCE: Animal models have shown altered dorsal cochlear nucleus circuitry in animals that develop tinnitus; however, precise treatment using bisensory (auditory and somatosensory) stimuli can reverse altered neural patterns and lessen tinnitus. OBJECTIVE: To confirm and extend the findings of a pilot study, which suggested an increased efficacy of bisensory stimulation, to a clinical trial with a greater duration and greater number of participants. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, crossover, single-center randomized clinical trial was conducted from March 2019, with a 3-month follow-up per participant ending in July 2022. Eligible adults were recruited from the University of Michigan Health System in Ann Arbor, Michigan. Eligibility criteria included bothersome tinnitus (Tinnitus Functional Index [TFI] score, ≥17 points), somatic tinnitus, normal to moderate hearing loss, and no other tinnitus treatments in the 6 months prior to the trial. Included participants were randomized to either treatment group 1, which received active (bisensory) treatment, or group 2, which received the control (auditory-only) treatment. Results were analyzed using intent-to-treat (ITT) and per protocol (PP) populations. INTERVENTION: Precisely timed bisensory (combined auditory and somatosensory) treatment was delivered through a portable, custom, take-home device that was provided to each participant for daily, at-home treatments. Group 1 participants received 30 minutes per day of the bisensory treatment for 6 weeks, followed by a 6-week washout phase, and then 30 minutes per day of the auditory-only treatment followed by a second 6-week washout phase. Group 2 participants received the auditory-only treatment first, followed by a washout phase, and then the bisensory treatment followed by a second washout phase. MAIN OUTCOMES AND MEASURES: Primary end points were changes in TFI score and tinnitus loudness level from baseline through week 6 and week 12. RESULTS: Of 337 screened individuals, 99 (mean [SD] age, 47 [12.7] years; 59 males [60%]; 85 with non-Hispanic White [86%] race and ethnicity) were enrolled into the study and randomized to treatment group 1 (n = 49) or group 2 (n = 50). The active but not the control treatment resulted in clinically significant decreases in TFI scores at week 6 of phase 1 (ITT population: -12.0 [95% CI, -16.9 to -7.9] points; P < .001; PP population: -13.2 [95% CI, -16.0 to -10.5] points; P < .001). Decreases in tinnitus loudness level were greater than 6 dB sensation level (SL; >half as loud) at week 6 for the bisensory treatment group, with little effect for the auditory-only treatment control group at week 6 of phase 1 (ITT population: -5.8 [95% CI, -9.5 to -2.2] dB; P = .08; PP population: -7.2 [95% CI, -11.4 to -3.1] dB; P = .03), and up to 11 dB SL at week 12 of phase 2 (ITT population: -10.9 [95% CI, -15.2 to -6.5] dB; P = .001; PP population: -14.1 [95% CI, -18.4 to -9.8] dB; P < .001). Decreased tinnitus loudness level and TFI scores extended into the washout phase, indicating a prolonged treatment effect. CONCLUSIONS AND RELEVANCE: This trial found that precisely timed bisensory treatment using stimuli and timing developed in a validated animal model was effective for adults with somatic tinnitus. Prolonged reduction in tinnitus symptoms can result from using an extended treatment duration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03621735.
重要性:动物模型显示,在发展为耳鸣的动物的背侧耳蜗核电路中存在改变;然而,使用双感觉(听觉和躯体感觉)刺激的精确治疗可以逆转改变的神经模式并减轻耳鸣。 目的:确认并扩展一项试点研究的结果,该研究表明双感觉刺激的疗效增加,从而进行了一项具有更大持续时间和更多参与者的临床试验。 设计、设置和参与者:这项双盲、交叉、单中心随机临床试验于 2019 年 3 月进行,每位参与者的随访期为 3 个月,截止到 2022 年 7 月。从密歇根大学健康系统招募符合条件的成年人,位于密歇根州安阿伯市。合格标准包括令人烦恼的耳鸣(耳鸣功能指数[TFI]评分,≥17 分)、躯体性耳鸣、正常至中度听力损失,以及在试验前 6 个月内没有其他耳鸣治疗。纳入的参与者被随机分配到治疗组 1(接受主动(双感觉)治疗)或组 2(接受对照(听觉仅)治疗)。使用意向治疗(ITT)和符合方案(PP)人群分析结果。 干预措施:通过一个便携式、定制、可在家中使用的设备提供精确计时的双感觉(听觉和躯体感觉组合)治疗,每个参与者都可在家中进行每日治疗。组 1 参与者每天接受 30 分钟的双感觉治疗,持续 6 周,然后是 6 周的洗脱期,然后是每天 30 分钟的听觉仅治疗,随后是第二个 6 周的洗脱期。组 2 参与者首先接受听觉仅治疗,然后进行洗脱期,然后接受双感觉治疗,然后进行第二个洗脱期。 主要结局和测量指标:主要终点是从基线到第 6 周和第 12 周时 TFI 评分和耳鸣响度水平的变化。 结果:在 337 名筛查个体中,有 99 名(平均[标准差]年龄,47[12.7]岁;59 名男性[60%];85 名非西班牙裔白人[86%]种族和民族)被纳入研究并随机分配到治疗组 1(n = 49)或组 2(n = 50)。活性但不是对照治疗导致第 1 阶段的第 6 周时 TFI 评分有临床意义的下降(ITT 人群:-12.0[95%CI,-16.9 至-7.9]分;P < .001;PP 人群:-13.2[95%CI,-16.0 至-10.5]分;P < .001)。在第 1 阶段的第 6 周,双感觉治疗组的耳鸣响度水平下降大于 6 分贝感觉水平(>一半音量),而听觉仅对照组的影响较小(ITT 人群:-5.8[95%CI,-9.5 至-2.2]dB;P = .08;PP 人群:-7.2[95%CI,-11.4 至-3.1]dB;P = .03),在第 2 阶段的第 12 周可达 11 分贝感觉水平(ITT 人群:-10.9[95%CI,-15.2 至-6.5]dB;P = .001;PP 人群:-14.1[95%CI,-18.4 至-9.8]dB;P < .001)。耳鸣响度水平和 TFI 评分的下降持续到洗脱期,表明治疗效果延长。 结论和相关性:这项试验发现,使用在经过验证的动物模型中开发的刺激和时间的精确双感觉治疗对有躯体性耳鸣的成年人有效。延长耳鸣症状的缓解可以通过延长治疗时间来实现。 试验注册:ClinicalTrials.gov 标识符:NCT03621735。
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