Microdosing initiation of buprenorphine for people seeking treatment for opioid use disorder

为寻求阿片类药物使用障碍治疗的人开始微剂量丁丙诺啡

• 批准号: 10670288
• 负责人: Benjamin T Hayes
• 金额: $ 19.42万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670288
• 关键词: Abstinence; Agonist; Anxiety; Area; Buprenorphine; Case Study; Cellular Phone; Clinical; Clinical Investigator; Clinical Trials; Data; Development; Development Plans; Dose; Dropout; Drug user; Ecological momentary assessment; Effectiveness; Electronics; Enrollment; Event; Focus Groups; Frequencies; Fright; Future; Goals; Health; Home; Hour; Impairment; Intervention; Interview; Investigation; Lesion; Literature; Measures; Mediating; Mediator; Mentors; Mentorship; Methods; Opioid; Opioid agonist; Outcome; Participant; Patients; Persons; Pharmacology; Physicians; Prevalence; Process; Process Measure; Protocols documentation; Provider; Qualitative Methods; Randomized; Randomized, Controlled Trials; Relapse; Research; Research Design; Research Personnel; Research Project Grants; Risk; Risk Reduction; Safety; Site; Symptoms; Technology Assessment; Testing; Therapeutic; Time; Training; Urine; Visit; Withdrawal; Withdrawal Symptom; Writing; anxiety symptoms; arm; barrier to care; buprenorphine treatment; career; career development; clinical care; craving; design; drug testing; efficacy testing; eligible participant; experience; feasibility trial; illicit opioid; improved; innovation; mortality; mu opioid receptors; opioid overdose; opioid use; opioid use disorder; opioid withdrawal; overdose death; participant enrollment; pilot test; primary outcome; recruit; safety and feasibility; secondary outcome; skills; standard care; substance use; success; treatment as usual; trial design; uptake

ABSTRACT With the career goal of becoming an independent physician-investigator, Dr. Benjamin Hayes describes a mentored research project and a rigorous career development plan which will prepare him to study the testing of interventions to improve the health of people who use drugs (PWUD). The prevalence of opioid use disorder (OUD) in the US has resulted in a marked spike in overdose deaths. Buprenorphine (BUP) treatment for opioid use disorder (OUD) reduces illicit opioid use and opioid overdose mortality, yet remains greatly underutilized. The initiation of BUP remains a major barrier to treatment uptake. Two challenges that limit BUP use are: 1) patients must typically avoid opioids for 24-48 hours before starting BUP, which results in a period of planned withdrawal symptoms; and 2) patients may experience preciptitated withdrawal during BUP initiation if taken too soon. Research has suggested that both types of withdrawal deter people from starting BUP and are reasons for initiation drop-out. Our goal is to rigorously develop and pilot test a “microdosing” protocol that overcomes the phamacologic challenges of buprenorphine treatment initiation. Microdosing is the process of starting buprenorphine at doses low enough to not precipitate withdrawal and incrementally increasing to therapeutic doses, at which point the patient stops their use full agonist opioids. We hypothesize that microdosing will increase buprenorphine treatment initiation success by (1) avoiding the need to experience withdrawal, and (2) reducing the risk of precipitated withdrawal. Case studies suggest that microdosing is feasible and may minimize withdrawal, but no randomized control trials of buprenorphine microdosing inititian have established safety and effectiveness. In a 4-week randomized controlled trial, we propose to pilot test an innovative buprenorphine microdosing protocol vs. treatment as usual (TAU), defined as standard home initiation of buprenorphine treatment. We will randomize 70 people with OUD to microdosing or TAU, conduct study visits at baseline and weeks 1 and 4, and provide participants with mobile phones to collect rich electronic Ecological Momentary Assessment (EMA) data. This proposal aims to 1) determine preliminary effectiveness, feasibility and safety and 2) stakeholder experiences to plan for a fully powered, multi-site RCT; and 3) use the EMA data to investigate whether symptoms of withdrawal, anxiety, and cravings mediate initiation success. These will inform the design of a fully powered RCT to test the efficacy of BUP microdosing initiation and enrich the literature of barriers to BUP initiation. To accomplish these aims, Dr. Hayes will pursue training in randomized controlled trial design and conduct, qualitative methods and analysis, EMA design, conduct, and analysis, and scientific writing. With completion of these activities, along with intensive mentorship, Dr. Hayes will develop the skills necessary to achieve his career goal of becoming an independent investigator.

摘要 本杰明·海斯博士的职业目标是成为一名独立的医生调查员，他描述了一种 指导的研究项目和严格的职业发展计划，这将使他准备研究测试 改善吸毒者健康的干预措施。阿片类药物使用障碍的患病率 (OUD)在美国导致了吸毒过量死亡的显著上升。丁丙诺啡（BUP）治疗阿片类药物 使用障碍（OUD）减少了阿片类药物的非法使用和阿片类药物过量死亡率，但仍然大大利用不足。 BUP的启动仍然是治疗吸收的主要障碍。限制BUP使用的两个挑战是：1） 患者通常必须在开始BUP之前避免阿片类药物24-48小时，这导致计划的一段时间 戒断症状;和2）如果服用BUP，患者可能在BUP启动期间出现戒断症状 太快了研究表明，这两种类型的撤退阻止人们开始BUP， 启动退出的原因。我们的目标是严格开发和试点测试一个“微剂量”协议 其克服了丁丙诺啡治疗起始的药理学挑战。微剂量是 以足够低的剂量开始丁丙诺啡的过程，以不引起戒断，并逐渐增加 增加到治疗剂量，此时患者停止使用完全激动剂阿片类药物。我们假设 微剂量将通过以下方式增加丁丙诺啡治疗开始的成功率：（1）避免需要 体验戒断，以及（2）降低突然戒断的风险。案例研究表明， 微量给药是可行的，可以最大限度地减少戒断，但没有丁丙诺啡的随机对照试验 微量给药已经确立了安全性和有效性。在为期4周的随机对照试验中，我们 建议对创新的丁丙诺啡微量给药方案与常规治疗（TAU）进行试点测试， 定义为丁丙诺啡治疗的标准家庭开始。我们将随机抽取70名OUD患者 在基线和第1周和第4周进行研究访视，并为参与者提供 移动的手机收集丰富的电子生态瞬时评估（EMA）数据。这项建议旨在 1)确定初步的有效性、可行性和安全性，2）利益相关者的经验，以计划全面的 有把握的多中心RCT; 3）使用EMA数据调查戒断症状，焦虑， 渴望介导启蒙的成功。这些将为设计一项充分把握度的RCT提供信息，以测试疗效 并丰富了BUP引发障碍的文献。为了实现这些目标， 博士Hayes将继续接受随机对照试验设计和实施、定性方法和 分析，EMA设计，行为和分析，以及科学写作。随着这些活动的完成，沿着 在密集的指导下，Hayes博士将发展必要的技能，以实现他的职业目标， 独立调查员