Neuromod Devices Limited, Dublin D08 R2YP, Ireland.
School of Medicine, Trinity College, Dublin D02 R590, Ireland.
Sci Transl Med. 2020 Oct 7;12(564). doi: 10.1126/scitranslmed.abb2830.
Tinnitus is a phantom auditory perception coded in the brain that can be bothersome or debilitating, affecting 10 to 15% of the population. Currently, there is no clinically recommended drug or device treatment for this major health condition. Animal research has revealed that sound paired with electrical somatosensory stimulation can drive extensive plasticity within the brain for tinnitus treatment. To investigate this bimodal neuromodulation approach in humans, we evaluated a noninvasive device that delivers sound to the ears and electrical stimulation to the tongue in a randomized, double-blinded, exploratory study that enrolled 326 adults with chronic subjective tinnitus. Participants were randomized into three parallel arms with different stimulation settings. Clinical outcomes were evaluated over a 12-week treatment period and a 12-month posttreatment phase. For the primary endpoints, participants achieved a statistically significant reduction in tinnitus symptom severity at the end of treatment based on two commonly used outcome measures, Tinnitus Handicap Inventory (Cohen's effect size: -0.87 to -0.92 across arms; < 0.001) and Tinnitus Functional Index (-0.77 to -0.87; < 0.001). Therapeutic improvements continued for 12 months after treatment for specific bimodal stimulation settings, which had not previously been demonstrated in a large cohort for a tinnitus intervention. The treatment also achieved high compliance and satisfaction rates with no treatment-related serious adverse events. These positive therapeutic and long-term results motivate further clinical trials toward establishing bimodal neuromodulation as a clinically recommended device treatment for tinnitus.
耳鸣是一种在大脑中编码的幻听感知，可能会令人烦恼或使人虚弱，影响 10% 至 15%的人群。目前，对于这种主要的健康状况，没有临床推荐的药物或设备治疗方法。动物研究表明，声音与电体感刺激相结合，可以驱动大脑中广泛的可塑性，用于耳鸣治疗。为了在人类中研究这种双模态神经调节方法，我们评估了一种非侵入性设备，该设备可向耳朵发送声音，并向舌头发送电刺激，这是一项随机、双盲、探索性研究，共纳入了 326 名患有慢性主观性耳鸣的成年人。参与者被随机分为三个平行臂，具有不同的刺激设置。临床结果在 12 周的治疗期和 12 个月的治疗后阶段进行评估。对于主要终点，根据两种常用的结局衡量标准，即耳鸣残疾量表（Cohen 的效应大小：-0.87 至-0.92，各臂之间；<0.001）和耳鸣功能指数（-0.77 至-0.87；<0.001），参与者在治疗结束时实现了耳鸣症状严重程度的统计学显著降低。对于特定的双模态刺激设置，治疗改善持续了 12 个月，而以前在大型耳鸣干预队列中并未证明这一点。该治疗还实现了高依从性和满意度，且无治疗相关的严重不良事件。这些积极的治疗和长期结果促使进一步开展临床试验，以确立双模态神经调节作为一种临床推荐的耳鸣设备治疗方法。
