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

通过经皮耳廓神经刺激改善同时发生的创伤后应激障碍和阿片类药物使用障碍患者的丁丙诺啡保留

• 批准号: 10775120
• 负责人: Joel Gregory Sprunger
• 金额: $ 58.22万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10775120
• 关键词: Acute; Address; Affective; Back; Buprenorphine; Caring; Clinic; Clinical; Clinical Trials; Communities; Data; Development; Devices; Diagnostic; Double-Blind Method; Dropout; Drops; Ear; Electric Stimulation; Electric Stimulation Therapy; Endorphins; Feasibility Studies; Feedback; Foundations; Heart Rate; Individual; Inpatients; Intervention; Measures; Medical; Methods; Motivation; Outcome; Overdose; Participant; Patient Recruitments; Patient Self-Report; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Population; Post-Traumatic Stress Disorders; Provider; Public Health; Quality of life; Randomized; Regulatory Pathway; Reporting; Research; Research Design; Risk; Sampling; Serious Adverse Event; Severities; Skin; Sparrows; Substance Use Disorder; Supervision; Symptoms; System; Techniques; Testing; Therapeutic; Time; Trigeminal System; Trigeminal nerve structure; Vagus nerve structure; Visit; Withdrawal Symptom; buprenorphine treatment; clinically significant; coping; craving; design; distress tolerance; effective therapy; experience; high risk; improved; innovation; medication for opioid use disorder; mortality risk; multilevel analysis; negative affect; noninvasive brain stimulation; open label; opioid overdose; opioid use; opioid use disorder; opioid withdrawal; pain sensation; phase II trial; portability; primary endpoint; primary outcome; randomized, clinical trials; recruit; reduce symptoms; response; secondary outcome; standard care; standard measure; substance use; time use; timeline; treatment comparison; vagus nerve stimulation

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.

项目摘要 背景。丁丙诺啡（BUP）是阿片类药物使用障碍（OUD）的有效药物，但辍学率 在稳定阶段（1-3个月）中很高。创伤后应激障碍（PTSD）在 因高伴侣和 强烈的负面影响大大增加了“自我药物”的冲动风险。经肌发射 迷走神经的神经刺激（TAN）已显示出减轻PTSD和Ooid符号的希望 戒断症状（OWS），但其作用尚未在样本开始bup疗法中进行测试 共同存在的关注点。 目标。我们将对拼这种sparrow上升系统进行开放标签试验（AIM 1; 2年UG3； n = 20） - A 患者管理的耳佩装置，将电刺激传递到迷走神经的分支和 三叉神经 - 评估棕褐色同时发生患者的可接受性，耐受性和可行性 PTSD/OUD在BUP计划的背景下。我们预计将保留超过50％的样本 bup。使用UG3研究中的数据，我们将完成FDA预提取的拟议UH3研究 支持麻雀的PTSD/OUD指示（AIM 2）。然后，我们将进行随机，意图对待， 假控制II期临床试验（AIM 3; 3年UH3; n = 60）测试TAN对BUP保留的影响 在PTSD/OUD患者中，以获取对TAN效果大小的现实估计，并为开发 随后进行全尺度临床试验。我们预计主动棕褐色将改善相对于假手术的bup保留率。 方法。对于这两项研究，我们都将在社区诊所招募患者启动BUP治疗，并 使用金标准测量值确认其PTSD/OUD诊断状态。患者将开始使用 在BUP感应后的一周内，麻雀上升设备。开放标签（UG3）研究的参与者和 主动棕褐色（UH3）条件将接受麻雀的治疗刺激；那些处于假状态 （UH3）不会。在开放标签试验中，我们将收集自我报告的耐受性和可行性 数据。对于这两项研究，我们都将获得自我报告和UDS确认的物质使用，BUP和麻雀 在3个月的活跃研究中，每周研究访问中的合规性以及自我报告的PTSD和OWS严重程度 时期。 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/不 保留）在数据提取时由当前的BUP处方定义。关键的次要结果 UG3试验包括抓链设备作为辅助设备的可接受性，耐受性和可行性 干预措施减轻了发起BUP的患者PTSD和OWS的症状。关键的次要结果 随机II期临床试验将包括每周使用时间表跟随和UDS 结果，PTSD符号的严重程度，阿片类药物的提取和渴望以及生活质量。