Digital Therapeutic Development of Virtual Cognitive-Affective Training for Opioid Use Disorder

项目摘要：美国正在经历阿片类药物危机，估计有250万美国人参加 阿片使用障碍的完整标准(OUD)。治疗阿片使用障碍(Moud)的药物有丁丙诺啡 目前对OUD最有效的干预形式。尽管Moud的功效已被证明，但近一半的人 开始患Moud的人会在六个月内复发。因此，新颖而有效的行为辅助手段 MUD是改善治疗结果所必需的。以正念为导向的康复强化(更多)， 通过NIDA资助的治疗开发过程产生的认知-情感训练干预已经 显示出显著的前景，在四个随机对照试验(RCT)中展示了治疗效果 减少阿片类药物的使用和误用，并调节药物线索反应和神经生理反应 自然奖励处理。然而，越多的干预需要大量的人类互动，并且 因此是资源密集型的。此外，鉴于新冠肺炎的流行，患有OUD的人可能会对 由于病毒传播的风险，需要进行面对面的干预。要克服这些实施障碍 并增加治疗的机会，拟议的项目将开发和测试虚拟现实版本的 更多干预(More-VR)建立在BehaVR LLC现有的商业可用的VR平台上 动态体验引擎(DXE)。DXE使用机器学习将生物识别技术集成到VR中 个性化治疗成瘾，提高患者参与度和优化治疗效果的经验 临床干预。在第一阶段，我们将在单臂临床研究中开发和测试More-VR原型 在阿片类药物治疗计划(OTP)中接受丁丙诺啡治疗的患者的比例，重点是患者的安全性和 订婚。如果原型被认为具有足够的可用性和净推动者分数，以及 在渴望和情感状态的近端测量方面产生改善，该项目将进入阶段 II.在第二阶段，我们将首先利用第一阶段的反馈开发更具虚拟现实的最低生存计划 研究以优化干预措施，然后像往常一样进行More-VR与Moud治疗的RCT。我们的 稳健和无偏倚的研究设计将使临床结果测量与生化测量三角 戒断的验证、生态瞬时评估(EMA)和神经生理学评估 提示-反应性。此外，我们将把More-VR计划整合到OTP运营环境中， FAST Healthcare Inter操作性Resources接口以从电子病历获取患者数据 (EMR)，并将患者利用率、评估和生物特征数据导出回EMR以创建患者 记录并告知临床医生患者的进展情况。第一阶段和第二阶段的活动将有助于定义 监管途径和建立监管可行性先于食品和药物管理局(FDA) More-VR系统被批准为II类医疗设备。总而言之，这个项目将把证据转化为- 以生物行为疗法为基础的创新数字疗法。

Project Summary: The US is experiencing an opioid crisis, with an estimated 2.5 million Americans meeting full criteria for opioid use disorder (OUD). Medications for opioid use disorder (MOUD) like buprenorphine are currently the most effective form of intervention for OUD. In spite of the proven efficacy of MOUD, nearly half of people who begin a MOUD relapse within six months. As such, novel and efficacious behavioral adjuncts to MOUD are needed to improve treatment outcomes. Mindfulness-Oriented Recovery Enhancement (MORE), a cognitive-affective training intervention generated through a NIDA-funded treatment development process has shown significant promise, demonstrating therapeutic effects in four randomized controlled trials (RCTs) by reducing opioid use and misuse and modulating neurophysiological responses during drug cue-reactivity and natural reward processing. However, the MORE intervention requires significant human interaction and is therefore resource intensive. Further, in light of the COVID-19 pandemic, people with OUD may be reticent to engage in face-to-face interventions due to the risk of viral spread. To overcome these implementation barriers and increase access to treatment, the proposed project will develop and test a virtual reality version of the MORE intervention (MORE-VR) built on BehaVR LLC's VR existing, commercially available platform, the Dynamic eXperience Engine (DXE). The DXE uses machine learning to integrate biometrics into the VR experience to personalize addictions treatment, boosting patient engagement and optimizing the efficacy of clinical intervention. In Phase I, we will develop and test the MORE-VR prototype in a single arm clinical study of OUD patients receiving buprenorphine in an opioid treatment program (OTP), focusing on patient safety and engagement. If the prototype is perceived to have adequate usability and Net Promoter Scores, as well as to produce improvements in proximal measures of craving and affective state, the project will progress to Phase II. In Phase II, we will first develop the MORE-VR Minimal Viable Program using feedback from our Phase I study to optimize the intervention, and then conduct a RCT of MORE-VR vs. MOUD treatment as usual. Our robust and unbiased research design will triangulate clinical outcome measurement with biochemical verification of abstinence, ecological momentary assessments (EMA), and neurophysiological assessment of cue-reactivity. Further, we will integrate the MORE-VR Program into the OTP operational environment, building Fast Healthcare Interoperability Resources interfaces to ingest patient data from electronic medical records (EMRs) and to export patient utilization, assessment, and biometric data back to EMRs to create patient records and inform clinicians of patient progress. Activities in Phase I and Phase II will help define the regulatory pathway and establish regulatory feasibility to precede Food and Drug Administration (FDA) approval of the MORE-VR system as a Class II medical device. In sum, this project will translate an evidence- based biobehavioral treatment approach into an innovative digital therapeutic for OUD.