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.

项目摘要 Evon Medics LLC建议评估和优化便携式家庭产品，计算机化 基于化学体的轨道额叶皮层训练（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）的患者。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，并反映出夸张的动力 消费药物和/或无法从事涉及非药品奖励的结果引导行为 食物，健康，社会地位和金钱。与过度吸毒相关的关联相反，非药物结果 通常不太确定，需要推断或精神模拟。眶额皮质（OFC） 通过提供关联结构（即认知图）在调节成瘾中起重要作用 对于这些心理模拟。此外，OFC通过增强在情感调节中起着至关重要的作用 负面情感线索的认知重新评估；负面影响是物质复发的有力预测指标。 OUD的人减少了OFC的数量和功能，海洛因和可卡因剂量依赖性降低 OFC神经元功能，从而加剧了复发药物的使用。 CBOT是一种编程，便携式，安全，用户友好的设备，用于连接化学感应 通过克服脱敏的刺激参数刺激OFC神经活动，对于 管理嗅觉认知任务，以高忠诚为协同地参与OFC，足以 诱导OFC功能的持久变化。第一阶段的研发达到或超过了 技术里程碑：CBOT干预导致结果引导的行为任务的表现提高， 在12周的随访期间，OUD患者的保留率增加了，并降低了复发率。 与假治疗相比，经CBOT治疗的OUD患者也经历了不太严重的阿片类药物戒断 和渴望，较少的睡眠中断和负面影响等级，与严重程度和持续时间无关 吸毒。 Evon Medics正在寻求SBIR II阶段资金，以证明其非 - 寻求和寻求治疗的OUD人群，从事长期，成功的阿片类药物 恢复。该建议将使其他产品的完善能够进行广泛的实施和 增加长期OUD治疗保留和禁欲的设备商业化 通过急性减少戒断严重程度和负面影响来增加参与恢复的参与。在 同时，Evon Medics正在参与战略合作伙伴关系，这些伙伴关系将用于推动发展 制造，监管文件，销售和分销。 Evon医师科学家，工程师和商业 专家是任务驱动的，并且具有高度动力，以影响全世界的心理和社会健康。 该第二阶段项目的关键技术目标是：（1）确定CBOT的有效性 在大量OUD受试者样本中，改善了保留率和预防复发； （2）确定其有效性 恢复早期的急性减少戒断严重程度和负面影响； （3）配置和优化 可改善功效，用户友好性和可接受性的商业就绪CBOT版本。这些目标 将导致优化的CBOT产品克服传统嗅觉疗法的缺点和其他 无创神经调节方法在治疗药物成瘾和预防复发方面。之上 II阶段的完成，我们将有望将研究扩展到第三阶段的功效研究，或 通过开发的商业合作伙伴关系实施在现实世界中的有效性研究 在这个项目的过程中。据我们所知，这将是对家庭的首次评估 可扩展，计算机化，基于化学的大脑刺激，对两种治疗的潜在广泛影响 - 寻求和非治疗寻求Oud人群。