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.

项目概要 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，但辍学率较高。 在稳定阶段（1-3 个月），创伤后应激障碍 (PTSD) 很常见。 患有 OUD 的个体，由于过度警觉和 强烈的负面影响会大大增加“自我治疗”冲动的风险。 迷走神经神经刺激 (tAN) 有望缓解 PTSD 和阿片类药物的症状 戒断症状 (OWS)，但其效果尚未在开始使用 BUP 治疗的样本中进行测试 同时发生的担忧。 我们将对 Sparrow Ascent 系统进行开放标签试验（目标 1；2 年 UG3；N = 20） 由患者操作的耳戴式设备，向迷走神经分支提供电刺激 三叉神经——评估 tAN 对于同时发生的患者的可接受性、耐受性和可行性 我们预计超过 50% 的样本将被保留在 BUP 启动的背景下。 BUP。使用 UG3 研究的数据，我们将完成 FDA 拟议的 UH3 研究的预提交 支持 Sparrow 的 PTSD/OUD 适应症（目标 2） 然后，我们将进行随机、意向治疗、 假手术对照 II 期临床试验（目标 3；3 年 UH3；N = 60）测试 tAN 对 BUP 保留的影响 在 PTSD/OUD 患者中进行研究，以获得 tAN 效应大小的实际估计，并为制定 我们预计，与假手术相比，活性 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接受 BUP 治疗的患者。 使用黄金标准措施确认他们的 PTSD/OUD 诊断状态 患者将开始使用 开放标签 (UG3) 研究的参与者在 BUP 诱导后一周内使用 Sparrow Ascent 装置。 活性 tAN (UH3) 条件将接受来自 Sparrow 的治疗刺激； (UH3) 不会。在开放标签试验期间，我们将收集自我报告和提供者报告的耐受性和可行性。 对于这两项研究，我们将自行报告并获得 UDS 确认的物质使用情况：BUP 和 Sparrow。 在为期 3 个月的主动研究中，每周研究访问中的依从性以及自我报告的 PTSD 和 OWS 严重程度 时期。 UG3 和 UH3 研究的主要结果是 3 个月的 BUP 保留率（保留/不保留）。 保留）如数据提取时当前 BUP 处方所定义。 UG3 试验包括 Sparrow 装置作为辅助手段的可接受性、耐受性和可行性 缓解开始 BUP 患者的 PTSD 和 OWS 症状的干预措施。 随机 II 期临床试验将包括每周的药物使用以及时间表随访和 UDS 结果、PTSD 症状严重程度、阿片类药物戒断和渴望以及生活质量。