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: 10267074
• 负责人: Steven L Batki
• 金额: $ 91.05万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10267074
• 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 过度饮酒是美国第三大死亡原因，约15个 百万美国人患有饮酒障碍（AUD）。 AUD在经济上也昂贵，有2490亿美元 每年花费与医疗保健，工作生产力失去的成本和犯罪有关的费用。尽管患病率很高 AUD及其严重后果，不到AUD的人不到20％接受任何治疗，主要是由于关键 当前治疗方案的缺点。 AUD治疗指南包括药物治疗，行为 干预，或两者兼而有之。荟萃分析始终证明一线AUD药物（Naltrexone和Naltrexone和 Acamprosate）充其量仅是适度有效的。 AUD药物治疗也具有常见的副作用 这限制了对患者的可接受性。与药物类似，行为干预，例如认知行为 治疗（CBT），仅提供小/中等的治疗益处。此外，程序通常需要节制， 这可能是一个障碍，因为许多AUD患者更喜欢非庇护目标。最近的临床前和临床研究 已经表明，周围神经途径的针灸可以显着调节渴望，奖励和 与滥用药物的戒断相关反应。因此，我们假设外周神经刺激可以是 通过直接影响渴望，奖励和退出的有效治疗方法。因此，Theranova 已经开发了授权神经调节系统，这是一种便携式，易于使用的经皮神经 用于非侵入性神经刺激的刺激（TENS）装置作为AUD的治疗。授权 神经调节系统由一个暂时的小型可穿戴控制器和凝胶电极组成 粘在皮肤上以刺激下面的神经。我们与AUD患者的I期临床研究证明 授权治疗可显着降低酒精消耗（平均还原= 29％，p = 0.026），酒精 渴望强度（平均降低21％，p = 0.001）和焦虑（平均还原= 31％，p <0.001）（相对于基线 每周测量）仅经过两周的治疗。虽然有前途，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，虚假控制的关键试验，以严格验证Empower提供了全面的权力 AUD处理。在该提案的目标1中，我们将首先更新授权神经调节系统的设计 并进行支持FDA提交所需的所有基准测试。然后，在AIM 2中，我们将进行多个 站点，假对照关键临床试验，以评估授权的安全性，有效性和可接受性为 AUD的治疗。通过这项工作获得的数据将支持FDA许可，使得 授权神经调节系统的商业化是AUD的全面处理。