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

项目总结 背景资料。丁丙诺啡(BUP)是治疗阿片类药物使用障碍(OUD)的有效药物，但脱落率较高 在稳定阶段(1-3个月)很高。创伤后应激障碍(PTSD)在 患有OUD和AND的个体由于过度兴奋和过度兴奋而使治疗中的保留变得更加困难 强烈的负面情绪极大地增加了“自我用药”的风险。经皮耳穴 迷走神经的神经刺激(TAN)已显示出缓解创伤后应激障碍和阿片类药物症状的希望 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 共同存在的担忧。 目标。我们将进行麻雀上升系统的开放标签试验(目标1；2年UG3；N=20)-a 患者使用的耳佩式装置，向迷走神经分支和迷走神经分支提供电刺激 三叉神经--评估三叉神经痛患者接受、耐受性和可行性的TAN 在BUP启动的背景下，创伤后应激障碍/OUD。我们预计50%以上的样品将被保留在 布普。使用UG3研究的数据，我们将完成FDA对拟议的UH3研究的预提交，以 支持麻雀创伤后应激障碍/OUD指征(目标2)。然后，我们将进行随机的意向治疗， 假对照II期临床试验(AIM 3；3年UH3；N=60)，测试Tan对BUP滞留的影响 在创伤后应激障碍/创伤后应激障碍患者中获得对Tan效应大小的真实估计，并告知A 随后进行了全面的临床试验。我们预计与假的相比，主动的Tan将改善BUP的保留。 方法：研究方法。对于这两项研究，我们将招募患者在社区诊所开始BUP治疗，并 使用黄金标准衡量标准确认他们的创伤后应激障碍/创伤后应激障碍诊断状态。患者将开始使用 麻雀上升装置在BUP诱导后一周内。开放标签(UG3)研究的参与者和 活跃的Tan(UH3)状态将接受Sparrow的治疗刺激；处于假状态的 (UH3)不会。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确认的物质使用情况、BUP和Sparrow 在为期3个月的积极研究中，每周访问研究时的遵从性和自我报告的创伤后应激障碍和OWS严重程度 句号。 结果。UG3和UH3研究的主要结果将是3个月的BUP保留(保留/不保留 保留)，如在数据提取时由当前BUP处方所定义。的主要次要结果 UG3试验包括Sparrow装置作为附件的可接受性、耐受性和可行性 干预缓解启动BUP患者的创伤后应激障碍和OWS症状。的主要次要结果 随机的第二阶段临床试验将包括每周一次的药物使用和时间表随访和UDS 结果，创伤后应激障碍症状严重程度、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.