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.

抽象的 过量饮酒是美国第三大死亡原因，大约 15 百万美国人患有酒精使用障碍（AUD）。澳元在经济上也很昂贵，达 2,490 亿美元 每年花费与医疗保健、工作效率下降和犯罪相关的费用。尽管患病率很高 AUD 及其严重后果，只有不到 20% 的 AUD 患者接受了任何治疗，这主要是由于关键因素 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，或两者兼而有之。荟萃分析一致表明，一线 AUD 药物（纳曲酮和 阿坎酸）充其量也只是中等程度的效果。 AUD 药物疗法也有常见的副作用 限制了患者的接受度。与药物治疗类似，行为干预，例如认知行为 疗法（CBT），仅提供小/中等的治疗益处。此外，项目通常要求禁欲， 这可能是一个障碍，因为许多 AUD 患者更喜欢非禁欲目标。最近的临床前和临床研究 研究表明，针灸周围神经通路可以显着调节渴望、奖赏和 滥用药物的戒断相关反应。因此，我们假设周围神经刺激可以 通过直接影响渴望、奖赏和戒断，AUD 成为一种有效的治疗方法。因此，TheraNova 开发了 Empower 神经调节系统，这是一种便携式、易于使用的经皮电神经 用于非侵入性神经刺激的刺激 (TENS) 装置作为 AUD 的治疗方法。赋权 神经调节系统由小型可穿戴控制器和临时凝胶电极组成 粘附在皮肤上，刺激下面的神经。我们对 AUD 患者进行的 I 期临床研究表明 Empower 治疗显着减少了饮酒量（平均减少量 = 29%，p=0.026） 渴望强度（平均减少 21%，p=0.001）和焦虑（平均减少=31%，p<0.001）（与基线相比） 周测量）仅在治疗两周后。虽然前景光明，但这是一项为期两周的开放标签研究， 因此，需要进行更长的、假对照的关键试验来严格验证 Empower 是否提供了全面的 澳元治疗。在该提案的目标1中，我们将首先更新Empower Neuromodulation System的设计 并进行支持 FDA 提交所需的所有实验室测试。然后，在目标 2 中，我们将进行多 现场、假对照关键临床试验，以评估 Empower 的安全性、有效性和可接受性 澳元的治疗方法。通过这项工作获得的数据将支持 FDA 的批准，使 Empower Neuromodulation System 的商业化作为 AUD 的综合治疗方法。