Assessing a Clinically-meaningful Opioid Withdrawal Phenotype

评估具有临床意义的阿片类药物戒断表型

• 批准号: 10580802
• 负责人: Kelly E Dunn
• 金额: $ 65.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580802
• 关键词: Attention; Behavioral; Buprenorphine; Categories; Classification; Clinical; Clinical Treatment; Clonidine; Data; Data Set; Development; Drug usage; Enrollment; Evaluation; Exposure to; Goals; Health Services Accessibility; Human; Individual; Individual Differences; Laboratories; Learning; Life Expectancy; Measurement; Morbidity - disease rate; Motivation; Naloxone; Naltrexone; Negative Reinforcements; Opioid; Opioid Antagonist; Opioid agonist; Outcome; Outpatients; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Physiological; Placebos; Positive Reinforcements; Provider; Public Health; Publishing; Reporting; Role; Sampling; Severities; Time; Tramadol; Withdrawal; Withdrawal Symptom; Woman; clinically relevant; design; experience; follow-up; lofexidine; medication for opioid use disorder; men; mortality; novel; opioid epidemic; opioid use disorder; opioid withdrawal; personalized medicine; prescription opioid; prospective; relapse prevention; response; secondary analysis; sex; treatment strategy; treatment trial

The US is in the midst of an opioid epidemic with rates of opioid-related morbidity and mortality so high they are decrementing average US life expectancy. The current need in the US for OUD treatment far exceeds the number of available treatment slots and treatment access is further complicated by the fact that not all patients respond in a similar way to our current OUD pharmacotherapies. We are experts in the measurement and evaluation of opioid withdrawal symptoms, the evaluation of novel medications for OUD treatment, and the assessment of individual differences in response to opioid medications. We recently conducted an analysis of a larger RCT that suggested patients could be classified into HIGH and LOW withdrawal phenotypes that were associated with the participant’s clinical response to OUD treatment medications in the subsequent RCT. This R01 will follow up on promising preliminary data we have published that suggests there are clinically- meaningful human opioid withdrawal phenotypes. We propose to conduct a rigorous, highly controlled human laboratory + spontaneous withdrawal study to verify and investigate these phenotypes. These data will advance opportunities for phenotype-driven opioid withdrawal management. We will enroll equal numbers of men and women who have OUD into a residential study. Participants will be stabilized onto an opioid agonist for a brief period, during which they will complete two naloxone challenges with a placebo or the OUD medication lofexidine, before beginning a clinical lofexidine-assisted taper and subsequent transition to the relapse prevention medication naltrexone. Primary aim 1 will identify opioid withdrawal phenotypes. We hypothesize that participants will separate into two latent classes that will be consistent with expressing a HIGH or LOW opioid withdrawal phenotype. Primary aim 2 will determine the degree to which naloxone challenge phenotype is associated with withdrawal during the subsequent clinical taper. We hypothesize that phenotype class during the naloxone challenge will be significantly associated with SOWS AUC values during the taper. Secondary Aim 1 will identify behavioral and physiological correlates of opioid withdrawal severity. We hypothesize that participants who experience varying levels of opioid withdrawal will show differences in behavioral (Subaim 1) or physiological (Subaim 2) correlates. Secondary Aim 2 will determine role of sex in withdrawal expression. We hypothesize that men and women will have different withdrawal severity (Aim 1), that withdrawal from the naloxone challenge session will correspond with withdrawal during the clinical taper in men and women (Aim 2), and that men and women will have different behavioral and physiological correlates with opioid withdrawal severity (Secondary Aim 1). Replicating our previous results by confirming presence of an opioid withdrawal phenotype will help advance personalized medicine approach to OUD, and understanding factors contributing to withdrawal severity (independent of phenotype) in men and women will expand opportunities for new medication development more broadly.

美国正处于卵毒素流行病中，与卵动物相关的发病率和死亡率如此之高 正在降低美国的平均预期寿命。美国目前对OUD治疗的需求远远超过 并非所有患者 与我们当前的OUD药物治疗的方式相似。我们是测量的专家 评估阿片类药物戒断症状，​​对OUD治疗的新药物的评估以及 评估对阿片类药物的响应的个体差异。我们最近对 建议患者可以分为高戒断表型的较大的RCT 与参与者在随后的RCT中对OUD治疗药物的临床反应有关。这 R01将跟进我们已经发布的有希望的初步数据，这表明有临床上的 有意义的人类阿片类药物戒断表型。我们建议进行严格，高度控制的人 实验室 +赞助戒断研究以验证和研究这些表型。这些数据将 通过表型驱动的阿片类药物戒断管理的预先机会。我们将注册相等的数字 曾经进入住宅研究的男人和女人。参与者将稳定在阿片类药物激动剂上 在短时间内，他们将通过安慰剂或Oud完成两个纳洛酮挑战 在开始临床洛芬辅助辅助锥度之前，药物洛夫己氨酸和随后过渡到 预防药物纳曲酮。主要目的1将识别阿片类药物戒断表型。我们 假设参与者将分为两个潜在类，这将与表达 高或低阿片类药物戒断表型。主要目标2将确定纳洛酮的程度 挑战表型与随后的临床胶带中的戒断有关。我们 假设在纳洛酮挑战期间的表型类将与母猪显着相关 磁带期间的AUC值。次要目标1将确定行为和身体上的相关性 Oopioid戒断严重程度。我们假设经历不同水平的绿o的参与者 提取将显示行为（Subaim 1）或物理（Subaim 2）的差异。次要 AIM 2将确定性别在戒断表达中的作用。我们假设男人和女人将拥有 不同的撤回严重程度（AIM 1），从纳洛酮挑战会话中提取的会议将与 在男性和女人的临床胶带期间提取（AIM 2），男人和女人将有不同的 行为和身体与阿片类药物的戒断严重程度相关（次要目标1）。复制我们的 通过确认阿片类药物提取表型的存在将有助于推进个性化的结果 医学方法的OUD方法，并了解导致戒断严重程度的因素（独立于 男性和女性的表型）将更广泛地扩大新药物开发的机会。