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、反复发作的疾病，影响着大约640万人 每年都有美国成年人。GAD是最常见的焦虑症之一，治疗费用昂贵，通过医疗手段 费用比其他焦虑症高出33%。美国人口普查局最近进行的每周GAD-2调查 该局表示，广泛性焦虑症的患病率可能会因为新冠肺炎的原因而急剧增加 大流行。截至2020年7月，36%的美国成年人有广泛性焦虑症的症状，而大流行前这一比例为8%。已被占用 总之，需要一种综合疗法来有效治疗广泛性焦虑症。广泛性AD的一线治疗 包括药物(如SSRIs、SNRI)、认知行为疗法，或两者兼而有之。不幸的是， 所有这些都显示出适度的长期缓解率，只有20%-50%。药物也有共同的， 限制患者接受度的不良副作用。苯二氮卓类药物(BZS)是最有效的 治疗广泛性焦虑症的药物。然而，指南建议只开短期使用的BZS，因为 培养宽容和依赖的潜力。重复性经颅神经调节研究 磁刺激(RTMS)最近在治疗广泛性AD方面显示出巨大的前景，有效率为- 100%在短期研究中。然而，rTMS价格昂贵(20-30个疗程6,000-12,000美元)和 需要每天到诊所就诊，限制了广泛采用的可能性。近期临床前和临床研究 研究还表明，基于针灸的神经刺激可以有效地治疗焦虑，但它 有一个关键的限制，即治疗必须由针灸医生在诊所或在家里进行。要建造 在这项工作中，并解决了对广泛性痴呆症综合治疗的需求，TheraNova开发了 赋能神经调节系统--一种便携式、非侵入性经皮神经电刺激 (TENS)，或经皮电针，用于非侵入性刺激周围神经的设备。这个 Empower神经调制系统由标准的、廉价的数十个凝胶电极和一个小电池组成- 供电的信号发生器。这项提议的目标是进行一项试验性的临床研究，以评估潜在的 作为广泛性痴呆症的治疗手段。我们将在30名参与者中进行为期6周的假对照研究， 盖德。参与者将被随机(1：1)分为积极或虚假治疗组和在家自我管理治疗组 在研究期间。在这项单独的研究中，我们将评估可行性指标(具体目标1)和 可接受性(具体目标2)。在论证了第一阶段的可行性后，我们将进行长期的枢纽 第二阶段临床试验，评估赋能疗法对广泛性焦虑症缓解的效果。这项关键的研究将 支持FDA批准，使第二阶段后实现商业化。

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.