Non-Invasive Neuromodulation Device for the Treatment of Alcohol Use Disorder

用于治疗酒精使用障碍的非侵入性神经调节装置

• 批准号: 10428659
• 负责人: David L Pennington
• 金额: $ 123.06万
• 依托单位: THERANOVA, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10428659
• 关键词: Abstinence; Acupuncture Points; Acupuncture Therapy; Adverse event; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcohols; American; Animals; Anxiety; Behavior Therapy; Brain; Cause of Death; Clinical; Clinical Research; Clinical Trials; Cognitive Therapy; Computer software; Consumption; Crime; Data; Development; Devices; Dopamine; Double-Blind Method; Effectiveness; Electrodes; Funding; Future; Gel; Goals; Guidelines; Healthcare; Heavy Drinking; High Prevalence; Home; Measurement; Meta-Analysis; Muscle; Naltrexone; Nerve; Nucleus Accumbens; Participant; Pathway interactions; Patients; Performance; Peripheral Nerve Stimulation; Peripheral Nerves; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Productivity; Randomized; Rewards; Risk; Rodent; Safety; Self Administration; Serious Adverse Event; Site; Skin; Small Business Innovation Research Grant; Structure of ulnar nerve; System; Testing; Transcutaneous Electric Nerve Stimulation; United States; Update; Withdrawal; Work; Wrist; acamprosate; active method; alcohol abuse therapy; alcohol craving; alcohol use disorder; base; biceps brachii muscle; commercialization; cost; craving; design; drinking; drug craving; drug of abuse; effective therapy; experience; medication compliance; meetings; neuroregulation; novel therapeutics; open label; portability; pre-clinical research; programs; prototype; research clinical testing; response; satisfaction; side effect; usability; verification and validation; wearable sensor technology

Abstract Excessive alcohol consumption is the third leading cause of death in the United States, and approximately 15 million Americans suffer from alcohol use disorder (AUD). AUD also economically expensive, with $249 billion spent annually for costs related to healthcare, lost work productivity, and crime. Despite the high prevalence of AUD and its severe consequences, less than 20% of those with AUD receive any treatment, mainly due to key drawbacks of current treatment options. Guidelines for AUD treatment include pharmacotherapy, behavioral intervention, or both. Meta-analyses consistently demonstrate that first-line AUD medications (naltrexone and acamprosate) are only moderately effective, at best. AUD pharmacotherapies also have common side effects that limit acceptability to patients. Similar to medications, behavioral interventions, such as cognitive behavioral therapy (CBT), provide only small/moderate treatment benefits. In addition, programs often require abstinence, which can be a barrier as many AUD patients prefer non-abstinent goals. Recent preclinical and clinical research has shown that acupuncture of a peripheral nerve pathway can significantly modulate craving-, reward-, and withdrawal-related responses for drugs of abuse. We, thus, hypothesize that peripheral nerve stimulation can be an effective treatment for AUD through its direct effects on craving, reward, and withdrawal. Thus, TheraNova has developed the Empower Neuromodulation System, a portable, easy-to-use transcutaneous electrical nerve stimulation (TENS) device for non-invasive nerve stimulation as a treatment for AUD. The Empower Neuromodulation System consists of a small, wearable Controller and gel electrodes that are temporarily adhered to the skin to stimulate the underlying nerve. Our Phase I clinical study with AUD patients demonstrated that the Empower treatment significantly reduced alcohol consumption (mean reduction = 29%, p=0.026), alcohol craving intensity (mean reduction 21%, p=0.001), and anxiety (mean reduction = 31%, p<0.001) (vs. baseline week measurements) after only two weeks of treatment. While promising, this was a two-week, open-label study, so a longer, sham-controlled pivotal trial is needed to rigorously verify that Empower offers a comprehensive AUD treatment. In Aim 1 of this proposal, we will first update the design of the Empower Neuromodulation System and conduct all bench testing required to support an FDA submission. Then, in Aim 2, we will conduct a multi- site, sham-controlled pivotal clinical trial to evaluate the safety, effectiveness, and acceptability of Empower as a treatment for AUD. The data obtained through this work will support FDA clearance, enabling commercialization of the Empower Neuromodulation System as a comprehensive treatment for AUD.

摘要 在美国，过度饮酒是导致死亡的第三大原因，约占 数百万美国人患有酒精使用障碍(AUD)。澳元在经济上也很昂贵，2490亿美元 每年用于与医疗保健、工作效率损失和犯罪相关的成本。尽管患病率很高，但 AUD及其严重后果，只有不到20%的AUD患者接受了治疗，主要是由于 当前治疗方案的缺点。AUD治疗指南包括药物治疗、行为治疗 干预，或者两者兼而有之。Meta分析一致表明，一线AUD药物(纳曲酮和 安非他明)充其量只能起到适度的效果。AUD药物疗法也有常见的副作用 这限制了患者的接受度。与药物类似，行为干预，如认知行为干预 治疗(CBT)，仅提供少量/中度治疗益处。此外，节食计划通常需要节欲， 这可能是一个障碍，因为许多AUD患者更喜欢非禁欲目标。最新的临床前和临床研究 已经表明，针刺外周神经通路可以显著调节渴望、奖励和 与药物滥用有关的戒断反应。因此，我们假设周围神经刺激可以是 通过其对渴望、奖励和戒断的直接影响，有效地治疗澳门氏症。因此，TheraNova 已经开发出赋能神经调制系统，这是一种便携式、易于使用的经皮电神经 非侵入性神经刺激(TENS)装置，用于治疗AUD。赋权 神经调节系统由一个小型的可穿戴控制器和凝胶电极组成，这些电极暂时 附着在皮肤上以刺激潜在的神经。我们对AUD患者进行的I期临床研究表明 赋能治疗显著降低了酒精消耗量(平均减少29%，p=0.026)， 渴求强度(平均减少21%，p=0.001)和焦虑(平均减少31%，p&lt；0.001)(对比基线 周测量)，仅治疗两周后。虽然前景看好，但这是一项为期两周的开放式研究， 因此，需要一个更长的、假对照的关键试验来严格验证Empower提供了一个全面的 AUD治疗。在本提案的目标1中，我们将首先更新授权神经调节系统的设计 并进行所有支持FDA提交的文件所需的台架测试。然后，在目标2中，我们将进行多项- 现场、假对照的关键临床试验，以评估Empower AS的安全性、有效性和可接受性 一种治疗澳元病的方法。通过这项工作获得的数据将支持FDA的批准，使 将Empower神经调节系统商业化，作为对AUD的综合治疗。