Empower Neuromodulation System, a home-use device for the treatment of anxiety disorders

摘要 广泛性焦虑症（GAD）是一种慢性复发性疾病，影响约640万人 美国成年人每年广泛性焦虑症是最常见的焦虑症之一，治疗费用昂贵， 比其他焦虑症患者高出33%。美国人口普查局最近的每周GAD-2调查 卫生局表示，由于COVID-19，GAD的患病率可能会急剧增加 流行病截至2020年7月，36%的美国成年人有GAD症状，而大流行前只有8%。采取 因此，需要一种有效治疗GAD的综合疗法。GAD的一线治疗 包括药物治疗（例如SSRIs、SNRIs）、认知行为治疗或两者的组合。不幸的是， 这些都显示出只有20- 50%的适度的长期缓解率。药物也有共同的， 限制患者接受的不良副作用。苯二氮卓类（BZ）是最有效的 治疗GAD的药物。然而，指南建议仅处方BZ用于短期使用， 发展耐受性和依赖性的潜力。通过重复经颅神经调节研究 磁刺激（rTMS）最近显示出治疗广泛性焦虑症的巨大希望，应答率为64- 100%在短期研究中。然而，rTMS是昂贵的（20-30个疗程6,000 - 12,000美元）， 需要每天去诊所，限制了广泛采用的可能性。近期临床前和临床 研究还表明，基于针刺的神经刺激可以有效治疗焦虑，但它 其主要局限性在于治疗必须由针灸师在诊所或家中进行。建立 在这项工作和解决需要一个全面的治疗广泛性焦虑症，TheraNova已经开发了 Empower神经调节系统，一种便携式、非侵入性经皮神经电刺激 （TENS）或经皮电针，用于非侵入性刺激外周神经的装置。的 Empower神经调节系统由标准、廉价的TENS凝胶电极和一个小型电池组成， 动力信号发生器该提案的目标是进行一项试点临床研究，以评估潜在的 作为广泛性焦虑症的治疗方法。我们将在30名参与者中进行为期6周的假对照研究， GAD。受试者将随机（1：1）接受活性药物或假治疗，并在家中自行给药 在研究期间。在这项研究中，我们将评估可行性指标（具体目标1）， 具体目标（2）。在第一阶段论证可行性后，我们将进行长期的关键性研究， II期临床试验，以评估Empower治疗对GAD缓解的影响。这项关键研究将 支持FDA批准，使第二阶段后的商业化。

Abstract Generalized anxiety disorder (GAD) is a chronic, recurring condition that affects approximately 6.4 million American adults each year. GAD is one of the most common anxiety disorders and is costly to treat, with medical costs that are 33% higher than other anxiety disorders. Recent weekly GAD-2 surveys by the U.S. Census Bureau have indicated that the prevalence of GAD may be sharply increasing as a result of the COVID-19 pandemic. As of July 2020, 36% of American adults have symptoms of GAD vs. 8% before the pandemic. Taken together, there is a need for a comprehensive therapy to effectively treat GAD. First-line treatments for GAD include medication (e.g. SSRIs, SNRIs), cognitive behavioral therapy, or both in combination. Unfortunately, these all have shown modest long-term remission rates of only 20-50%. Medications also have common, undesirable side effects that limit acceptability to patients. Benzodiazepines (BZs) are the most effective medication for treating GAD. However, guidelines recommend only prescribing BZs for short-term use due to the potential to develop tolerance and dependence. Neuromodulation investigations via repetitive transcranial magnetic stimulation (rTMS) have recently shown great promise for treating GAD, with responder rates of 64- 100% in short-term studies. However, rTMS is expensive ($6,000-$12,000 for a 20-30 treatment course) and requires daily visits to the clinic, limiting the potential for widespread adoption. Recent preclinical and clinical studies have also shown that acupuncture-based nerve stimulation can be effective for treating anxiety, but it has the key limitation that treatment must be administered by an acupuncturist in the clinic or at home. To build on this work and address the need for a comprehensive therapy for GAD, TheraNova has developed the Empower Neuromodulation System, a portable, non-invasive transcutaneous electrical nerve stimulation (TENS), or transcutaneous electroacupuncture, device for non-invasive stimulation of peripheral nerves. The Empower Neuromodulation System consists of standard, inexpensive TENS gel electrodes and a small, battery- powered signal generator. The goal of this proposal is to conduct a pilot clinical study to evaluate the potential of Empower as a treatment for GAD. We will conduct a 6-week, sham-controlled study in 30 participants with GAD. Participants will be randomized (1:1) to the active or sham treatment and self-administer treatment at home for the duration of the study. In this single study, we will evaluate metrics of feasibility (Specific Aim 1) and acceptability (Specific Aim 2). After demonstrating feasibility in Phase I, we will conduct a long-term pivotal clinical trial in Phase II to evaluate the effect of the Empower therapy on GAD remission. This pivotal study will support FDA clearance, enabling commercialization after Phase II.