Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) for Opioid Use Disorder

针对阿片类药物使用障碍的基于计算机化化学感应的眶额皮层训练 (CBOT) 的开发和评估

• 批准号: 10268251
• 负责人: Evaristus A Nwulia
• 金额: $ 85.91万
• 依托单位: EVON MEDICS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268251
• 关键词: Abstinence; Acute; Address; Adult; Animal Model; Base of the Brain; Behavior; Behavior Therapy; Behavioral; Brain; Brain region; Buprenorphine; Categories; Clinic; Clinical Trials; Cocaine; Cognitive; Collaborations; Consumption; Continuity of Patient Care; Cost Savings; Cues; Data; Data Set; Development; Devices; Disease; Dose; Drug Addiction; Drug Controls; Drug usage; Educational Intervention; Effectiveness; Engineering; Epidemic; Evaluation; Failure; Family; Feedback; Food; Funding; Future; Grant; HIV/HCV; Health; Health Status; Heroin; Hippocampus (Brain); Home; Impairment; Individual; Institution; Intervention; Intervention Studies; Lead; Life; Location; Maintenance; Maintenance Therapy; Manufacturer Name; Maps; Marketing; Mission; Moods; Morbidity - disease rate; Neurons; Neurosciences; Odors; Olfactory Cortex; Opioid; Opioid replacement therapy; Outcome; Pain; Patients; Performance; Pharmaceutical Preparations; Phase; Placebos; Play; Population; Prevention; Psyche structure; Randomized; Recovery; Recurrence; Regimen; Regulation; Relapse; Research; Role; Sales; Sampling; Scientist; Sensory; Severities; Sleep; Sleep disturbances; Small Business Innovation Research Grant; Social status; Societies; Structure; Substance Use Disorder; System; Time; Training; Translational Research; United States; Virus Diseases; Withdrawal; addiction; base; cocaine use; cognitive enhancement; cognitive reappraisal; cognitive task; cognitive training; commercialization; comorbidity; comparison intervention; computerized; cost; craving; desensitization; design; disorder later incidence prevention; drug abuse prevention; drug seeking behavior; effectiveness implementation study; efficacy study; emotion regulation; experience; falls; follow-up; habituation; implementation study; improved; injection drug use; innovation; intervention effect; mortality; negative affect; neuroregulation; non-drug; olfactory stimulus; opioid use; opioid use disorder; opioid withdrawal; overtreatment; portability; preconditioning; prescription opioid; prevent; programs; prospective; randomized trial; relating to nervous system; research and development; retention rate; simulation; social; success; usability; user-friendly

PROJECT SUMMARY Evon Medics LLC proposes to evaluate and optimize the portable, home-based product, Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT), as an alternative strategy for relapse prevention in patients with Opioid Use (OUD) and other substance use disorders (SUD). Opioid and other forms of drug addiction can be defined as a failure to control drug-seeking behavior, and reflect an exaggerated drive to consume drugs, and/or an inability to engage in outcome-guided behaviors involving non-drug rewards such as food, health, social status and money. In contrast to overlearned drug-related associations, non-drug outcomes are often less well established and need to be inferred or mentally simulated. The orbitofrontal cortex (OFC) plays important role in regulation of addiction through provision of an associative structure (i.e. cognitive map) for these mental simulations. Additionally, the OFC plays critical role in emotion regulation through enhanced cognitive reappraisal of negative affective cues; and negative affect is a strong predictor of substance relapse. People with OUD have reduced OFC volume and function, and heroin and cocaine dose-dependently diminish OFC neuronal functions, thereby fueling recurrent drug use. The CBOT is a programmed, portable, safe, user-friendly device for conjoined chemosensory stimulation of OFC neural activity with stimulation parameters that overcome OFC desensitization, and for administration of olfactory cognitive tasks that synergistically engage the OFC with high fidelity sufficient to induce lasting changes in OFC functions. Phase I research and development met or exceeded stated technical milestones: CBOT intervention led to increased performance in outcome-guided behavior tasks, increased retention of OUD patients in treatment and reduced relapse rate during 12 weeks follow-up. Compared to sham treatment, CBOT-treated OUD patients also experienced less severe opioid withdrawal and cravings, and less sleep disruptions and negative affect rating, independent of severity and duration of drug use. Evon Medics is seeking SBIR Phase II funding to demonstrate its utility for home application by non- treatment seeking and treatment-seeking OUD populations, to engage in long-term, successful opioid recovery. This proposal will enable additional product refinement to allow broad implementation and commercialization of the device that increases long-term OUD treatment retention and abstinence and increases engagement in recovery through acute reduction of withdrawal severity and negative affect. At the same time, Evon Medics is engaging strategic partnerships that will be used to drive development through manufacturing, regulatory filings, sales, and distribution. Evon Medics scientists, engineers and commercial experts are mission-driven and highly motivated to make an impact on mental and social health worldwide. Key technical objectives of this Phase II project are to: (1) establish the effectiveness of CBOT for improved retention and relapse prevention in a large sample of OUD subjects; (2) establish its effectiveness for acute reduction of withdrawal severity and negative affect early in recovery; and (3) configure and optimize a commercial-ready CBOT version for improved efficacy, user-friendliness and acceptability. These objectives will lead to an optimized CBOT product that overcomes the drawbacks of traditional olfactory therapy and other noninvasive neuromodulation approaches in the treatment of drug addictions and prevention of relapses. Upon completion of Phase II, we will be poised to expand the research to Phase III efficacy study, or an implementation study of effectiveness in the real-world setting through commercial partnerships developed over the course of this project. To the best of our knowledge, this will be the first evaluation of a home-based, scalable, computerized, chemosensory-based brain stimulation with potential broad impact for both treatment- seeking and non-treatment seeking OUD populations.

项目概要 Evon Medics LLC 提议评估和优化便携式家用产品“计算机化” 基于化学感应的眶额皮层训练 (CBOT)，作为预防复发的替代策略 阿片类药物使用 (OUD) 和其他物质使用障碍 (SUD) 患者。阿片类药物和其他形式的药物 成瘾可以定义为无法控制寻求毒品的行为，并反映了过度的追求毒品的冲动。 吸毒，和/或无法参与涉及非药物奖励的结果导向行为，例如 食物、健康、社会地位和金钱。与过度了解的药物相关关联相比，非药物结果 通常不太确定，需要推断或心理模拟。眶额皮质 (OFC) 通过提供联想结构（即认知图）在成瘾调节中发挥重要作用 对于这些心理模拟。此外，OFC 通过增强情绪调节在情绪调节中发挥着关键作用。 对负面情感线索的认知重新评估；负面情绪是物质复吸的有力预测因素。 患有 OUD 的人 OFC 体积和功能减少，海洛因和可卡因剂量依赖性减少 OFC 神经元功能，从而助长反复吸毒。 CBOT 是一种可编程、便携式、安全、用户友好的联合化学感应设备 使用克服 OFC 脱敏的刺激参数刺激 OFC 神经活动，并用于 嗅觉认知任务的管理，协同地使 OFC 具有足够的高保真度 引起 OFC 功能的持久变化。一期研发达到或超过规定 技术里程碑：CBOT 干预提高了以结果为导向的行为任务的绩效， 增加了 OUD 患者的治疗保留率并降低了 12 周随访期间的复发率。 与假治疗相比，CBOT 治疗的 OUD 患者的阿片类药物戒断症状也较轻 和渴望，以及更少的睡眠中断和负面情绪评级，与严重程度和持续时间无关 药物使用。 Evon Medics 正在寻求 SBIR 第二阶段资金，以证明其对于非家庭应用的实用性 寻求治疗和正在寻求治疗的 OUD 人群，参与长期、成功的阿片类药物治疗 恢复。该提案将进一步完善产品，以实现广泛实施和 该装置的商业化可提高长期 OUD 治疗保留率和戒断率，以及 通过急剧减少戒断严重程度和负面影响来增加康复的参与度。在 与此同时，Evon Medics 正在建立战略合作伙伴关系，通过以下方式推动发展： 制造、监管备案、销售和分销。 Evon Medics 的科学家、工程师和商业人士 专家们以使命为导向，积极主动地对全世界的心理和社会健康产生影响。 第二阶段项目的关键技术目标是： (1) 建立 CBOT 的有效性 改善大样本 OUD 受试者的保留和复发预防； (2) 确定其有效性 戒断严重程度和康复早期负面影响急剧减轻； (3) 配置和优化 商业就绪的 CBOT 版本可提高功效、用户友好性和可接受性。这些目标 将产生一种优化的 CBOT 产品，克服传统嗅觉疗法和其他疗法的缺点 非侵入性神经调节方法治疗毒瘾和预防复发。之上 II 期完成后，我们将准备将研究扩展到 III 期疗效研究，或者 通过建立商业伙伴关系，对现实世界中的有效性进行实施研究 在这个项目的过程中。据我们所知，这将是对家庭式、 可扩展的、计算机化的、基于化学感应的脑刺激对治疗和治疗都有潜在的广泛影响 寻求和不寻求治疗的 OUD 人群。