Combined tDCS and Cognitive Training for the Treatment of Opioid Addiction

有证据表明，认知训练可以改善阿片类药物成瘾者的认知能力， 本研究的主要目的是测试经颅直流电是否 刺激（tDCS）可用于提高认知训练在增强阿片类药物认知方面的有效性 使用障碍来改善OUD治疗结果。UG 3阶段定位于FDA的第1阶段 调节途径，我们将首次测试tDCS +认知训练在一个 使用RCT设计的阿片类药物使用障碍（OUD）人群。UG 3的目标是确定 干预：（A1）安全可行，（A2）以剂量依赖性方式诱导基于回路的靶点接合， （A3）提高认知能力。我们将研究（A4）变化之间的关系， 认知和基于电路的目标的变化。UG 3的结果将为UH 3的设计细节提供信息。 UH 3阶段将处于FDA监管途径的第2阶段。UH 3目标将扩展UG 3目标 通过检查干预对（A5）临床疗效（减少阿片类药物使用）、（A6） 目标参与、认知和临床功效，以及（A7）探索个体建模的调节效应 tDCS电场。在UH 3阶段结束时，我们应该能够设计另一个阶段2， 支持上市前批准申请的3项临床试验。我们的双盲随机对照设计 通过让所有参与者随机接受认知训练， 活性或假tDCS。在UG 3阶段，将招募30名OUD受试者，研究 tDCS剂量通过对比接受5次与10次活性tDCS治疗的患者。脑成像， 认知和行为测量将进行三次：基线时、5次治疗后和10次治疗后 sessions.在干预后1个月和2个月收集随访的认知和行为指标。 这将使我们能够检查目标参与，以及认知和行为影响。UG 3里程碑 是证明：安全性，可行性，目标参与，和认知的改善。结果 UG 3将确定UH 3的治疗疗程数。在UH 3阶段，将有100名参与者 招募来确定临床疗效和耐久性。大脑成像，认知和行为测量将 进行三次：基线时、干预后和1个月随访时。这将使我们能够 检查临床疗效（减少阿片类药物的使用）和干预的持久性。UH 3的里程碑是 证明：临床有效性、持久性、目标接合与测量之间的关系 认知和药物使用行为（减少阿片类药物使用）。冲击认知障碍及其潜在的 神经机制影响成瘾治疗的结果。我们建议进行第一项研究，以探讨如何tDCS- 增强认知训练影响阿片类药物使用障碍的认知及其相关脑回路， 为未来的大规模临床试验做准备。

Evidence suggests that cognitive training can improve cognition in individuals with opioid addiction and may improve treatment outcome.The primary objective of this study is to test whether transcranial direct current stimulation (tDCS) can be used to boost the effectiveness of cognitive training in enhancing cognition in opioid use disorder to improve OUD treatment outcome. The UG3 phase is positioned to be in Phase 1 of the FDA Regulatory Pathway in which we will test for the first time the intervention of tDCS + cognitive training in a population with opioid use disorder (OUD) using an RCT design. The UG3 Aims are to determine if the intervention: (A1) is safe and feasible, (A2) induces circuit-based target engagement in a dose dependent manner, (A3) produces improvement in cognition. We will examine (A4) the relationship between changes in cognition and changes in the circuit-based target. Results from the UG3 will inform design details for the UH3. The UH3 phase will be in Phase 2 of the FDA Regulatory Pathway. The UH3 Aims will expand on UG3 aims by examining the effect of the intervention on (A5) clinical efficacy (decreased opioid use), (A6) durability of target engagement, cognition and clinical efficacy, and (A7) explore moderation effect of individually modeled tDCS electric field. At the end of the UH3 phase, we should be positioned to design either a further Phase 2 or 3 Clinical Trial to support a Premarket Approval application. Our double-blind randomized controlled design controls for participant effort and time by having all participants receive cognitive training with randomization to either active or sham tDCS. In the UG3 phase, 30 participants with OUD will be recruited to study the effect of tDCS dose by contrasting those that received 5 vs 10 treatment sessions of active tDCS. Brain imaging, cognitive and behavioral measures will be conducted three times: at baseline, after 5 sessions, and after 10 sessions. Follow-up cognitive and behavioral measures will be collected 1 and 2 months after intervention. This will allow us to examine target engagement, as well as cognition and behavior effects. UG3 milestones are the demonstration of: safety, feasibility, target engagement, and improvement in cognition. Results from the UG3 will determine the number of treatment sessions.for UH3. In the UH3 phase, 100 participants will be recruited to determine clinical efficacy and durability. Brain imaging, cognitive and behavioral measures will be conducted three times: at baseline, after the intervention, and at 1 month follow-up. This will allow us to examine clinical efficacy (decreased opioid use) and durability of the intervention. Our milestones for UH3 are the demonstration of: clinical efficacy, durability, relationship between target engagement and measures of cognition and drug use behavior (decreased opioid use). Impact. Cognitive impairments and its underlying neural mechanisms affect addiction treatment outcomes. We propose the first study to examine how tDCS- augmented cognitive training affects cognition and its related brain circuitry in opioid use disorder, setting the stage for future large scale clinical trials.