Improving Buprenorphine Retention with Transcutaneous Auricular Neurostimulation for Patients with Co-occurring Posttraumatic Stress Disorder and Opioid Use Disorder

项目摘要 背景丁丙诺啡（BUP）是治疗阿片类药物使用障碍（OUD）的有效药物， 在稳定阶段（1-3个月），创伤后应激障碍（PTSD）是常见的， OUD患者，由于过度觉醒和 强烈负面影响会大大增加“自我克制”的风险。经皮耳廓 迷走神经的神经刺激（tAN）已经显示出减轻PTSD和阿片类药物的症状的希望。 戒断症状（OWS），但其效果尚未在开始BUP治疗的样本中进行测试， 共同发生的问题。 目标。我们将对Sparrow Ascent系统进行一项开放标签试验（目标1; 2年UG 3; N = 20）-a 患者给药的耳戴式设备，其向迷走神经的分支递送电刺激， 三叉神经-评估tAN对合并有神经系统疾病的患者的可接受性、耐受性和可行性。 BUP启动背景下的PTSD/OUD。我们预计，超过50%的样本将保留在 呸。使用UG 3研究的数据，我们将完成拟议UH 3研究的FDA预提交， 支持Sparrow的PTSD/OUD指示（目标2）。然后，我们将进行一个随机的，意向性治疗， 测试tAN对BUP保持的影响的假对照II期临床试验（Aim 3; 3年UH 3; N = 60） 在PTSD/OUD患者中，以获得对tAN效应大小的现实估计，并告知 随后进行全面临床试验。我们预计，相对于假手术，主动tAN将改善BUP保留。 方法.对于这两项研究，我们将招募在社区诊所开始BUP治疗的患者， 使用金标准措施确认他们的PTSD/OUD诊断状态。患者将开始使用 在BUP诱导后一周内使用Sparrow Ascent器械。开放标签（UG 3）研究的受试者和 活性tAN（UH 3）条件下将接受Sparrow的治疗刺激;假条件下的治疗刺激 (UH3)不会的在开放标签试验期间，我们将收集自我和提供者报告的耐受性和可行性 数据对于这两项研究，我们将获得自我报告和UDS确认的物质使用，BUP和Sparrow 在为期3个月的积极研究中，每周研究访视时的依从性和自我报告的PTSD和OWS严重程度 期 结果。UG 3和UH 3研究的主要结局是3个月BUP保留（保留/未保留） 保留），如数据提取时当前BUP规定所定义。关键次要结局 UG 3试验包括Sparrow器械作为辅助器械的可接受性、耐受性和可行性 干预缓解BUP患者的PTSD和OWS症状。关键次要结局 随机化II期临床试验将包括每周药物使用情况、时间轴随访和UDS 结果，PTSD症状严重程度，阿片类药物戒断和渴求，以及生活质量。

PROJECT SUMMARY Background. Buprenorphine (BUP) is an effective medication for opioid use disorder (OUD) but dropout rates are high during the stabilization phase (months 1-3). Posttraumatic stress disorder (PTSD) is common in individuals with OUD and makes retention in treatment even more challenging because of hyperarousal and intense negative affect that greatly increase risk for urges to “self-medicate”. Transcutaneous auricular neurostimulation (tAN) of the vagus nerve has shown promise for alleviating symptoms of PTSD and opioid withdrawal symptoms (OWS) but its effects have yet to be tested in a sample starting BUP therapy with these co-occurring concerns. Aims. We will conduct an open-label trial (Aim 1; 2-year UG3; N = 20) of the Sparrow Ascent System—a patient-administered, ear worn device that delivers electrical stimulation to branches of the vagus and trigeminal nerves—to evaluate the acceptability, tolerability, and feasibility of tAN for patients with co-occurring PTSD/OUD in the context of BUP initiation. We anticipate that more than 50% of the sample will be retained in BUP. Using data from the UG3 study, we will complete FDA pre-submission for the proposed UH3 study to support a PTSD/OUD indication for Sparrow (Aim 2). Then, we will conduct a randomized, intent-to-treat, sham-controlled Phase II clinical trial (Aim 3; 3-year UH3; N = 60) testing the effects of tAN on BUP retention among PTSD/OUD patients to obtain realistic estimates of tAN’s effect size and inform development of a subsequent full-scale clinical trial. We anticipate that active tAN will improve BUP retention relative to sham. Methods. For both studies, we will recruit patients initiating BUP treatment in a community-based clinic and confirm their PTSD/OUD diagnostic status using gold-standard measures. Patients will begin using the Sparrow Ascent device within one week of BUP induction. Participants in the open-label (UG3) study and active tAN (UH3) conditions will receive therapeutic stimulation from Sparrow; those in the sham condition (UH3) will not. During the open-label trial, we will collect self- and provider-reported tolerability and feasibility data. For both studies, we will obtain self-reported and UDS-confirmed substance use, BUP and Sparrow compliance, and self-reported PTSD and OWS severity at weekly research visits over the 3-month active study period. Outcomes. The primary outcome in the UG3 and UH3 studies will be 3-month BUP retention (retained/not retained) as defined by current BUP prescription at the time of data extraction. Key secondary outcomes for the UG3 trial include the acceptability, tolerability, and feasibility of the Sparrow device as an adjunct intervention alleviating symptoms of PTSD and OWS for patients initiating BUP. Key secondary outcomes for the randomized Phase II clinical trial will include weekly substance use with timeline follow-back and UDS results, PTSD symptom severity, opioid withdrawal and craving, and quality of life.