University of Michigan BACPAC Mechanistic Research Center

密歇根大学BACPAC机理研究中心

• 批准号: 10765807
• 负责人: Daniel J Clauw
• 金额: $ 219.98万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10765807
• 关键词: University; Michigan; BACPAC; Mechanistic; Research

PROJECT SUMMARY / ABSTRACT OVERALL COMPONENT The NIH BACPAC initiative is designed to “generate new knowledge regarding phenotypes, endotypes, mechanisms, diagnostics, trial outcomes, and therapeutic responsiveness . . . in chronic low back pain (cLBP). We feel that our group at the University of Michigan (UM) is ideally suited to lead a Mechanistic Research Center (MRC) as part of the broader BACPAC initiative, because we have been working along all of these lines for over twenty years. We propose a single Research Project that will take patients with cLBP and use a patient-centric, SMART design study to follow these individuals longitudinally as they try several different evidence-based therapies, while mechanistic studies are overlaid to draw crucial inferences about what treatments will work in what patient endotypes. We use the term Interventional Response Phenotyping to describe the need in any precision medicine initiative to phenotype participants regarding what therapies they do and do not respond to - so that one can later link mechanistically distinct disease endophenotypes with those who preferentially respond to therapies targeting those mechanisms. The first Specific Aim of the UM BACPAC MRC is to perform Interventional Response Phenotyping in a cohort of cLBP patients (n=500). We will perform a long-term pragmatic trial using a well-established cohort of cLBP patients, who will receive a sequence of interventions known to be effective in cLBP. All cLBP participants will for the first 6 weeks receive a web-based patient self-management program for pain. This first treatment period is not testing mechanistic hypotheses, but instead will reduce or eliminate regression to the mean, as well as the placebo effect of interacting with staff, prior to subsequent randomized treatments. Then participants who remain symptomatic will be enrolled in an adaptive, Sequential Multiple Assessment Randomized Trial (SMART) to randomize individuals to two additional treatments given for 12 weeks each, from a list including: a) mindfulness-based cognitive therapy (MBCT); b) physical therapy and exercise; c) duloxetine, d) gabapentin and e) self- administered acupressure. At any point during the study, participants (as part of ongoing care) may also undergo an epidural steroid or facet joint injection, or lumbar surgery. Although participants will not be randomized to receive these interventional therapies, we can assess for predictors of differential responsiveness. The second Specific Aim of this proposal is to demonstrate that currently available, clinically- derived measures, can predict differential responsiveness to the above therapies (n=500). The third Specific Aim is to identify new experimental measures (functional neuroimaging, quantitative sensory testing, plasma measures of inflammation, autonomic tone) that predict differential responsiveness to the each of the therapies, as well as to infer mechanisms of action of treatments (n=200). The fourth Specific Aim is to contribute to the broader BACPAC initiative by providing data on our MRC participants, as well as contributing scientific expertise, research methods, and leadership to BACPAC.

项目概要/摘要 整体组成 NIH BACPAC 计划旨在“产生有关表型、内型、 慢性腰痛 (cLBP) 的机制、诊断、试验结果和治疗反应。 我们认为我们密歇根大学 (UM) 的团队非常适合领导机械研究 中心 (MRC) 作为更广泛的 BACPAC 计划的一部分，因为我们一直在沿着所有这些方向开展工作 二十多年来，我们提出了一个单一的研究项目，该项目将针对 cLBP 患者并使用 以患者为中心的 SMART 设计研究，纵向跟踪这些人尝试几种不同的方法 基于证据的疗法，同时叠加机制研究以得出关于什么的重要推论 治疗将在什么患者的内型上起作用我们使用术语“介入反应表型分析”。 描述任何精准医学计划对表型的需求，以了解他们采用的疗法 做和不做反应 - 以便以后可以将机械上不同的疾病内表型与 那些优先响应针对这些机制的治疗的人。 UM 的第一个具体目标。 BACPAC MRC 将对一组 cLBP 患者 (n=500) 进行干预反应表型分析。 将使用成熟的 cLBP 患者队列进行一项长期务实试验，这些患者将接受 所有 cLBP 参与者将在前 6 周接受已知对 cLBP 有效的干预措施。 一个基于网络的患者疼痛自我管理计划。第一个治疗期并不是测试机制。 假设，但会减少或消除均值回归，以及安慰剂效应 在随后的随机治疗之前与工作人员互动，然后是仍然有症状的参与者。 将参加适应性序贯多重评估随机试验 (SMART) 以进行随机分组 个人接受两次额外治疗，每次 12 周，治疗清单包括：a) 基于正念的治疗 认知治疗（MBCT）；b) 物理治疗和锻炼；c) 度洛西汀，d) 加巴喷丁和 e) 自我治疗 在研究期间的任何时候，参与者（作为持续护理的一部分）也可以进行穴位按摩。 接受硬膜外类固醇或小关节注射，或腰椎手术，但参与者不会。 随机接受这些介入治疗，我们可以评估差异的预测因子 该提案的第二个具体目标是证明目前可用的临床- 衍生的测量，可以预测对上述疗法的不同反应（n = 500）。 目的是确定新的实验措施（功能神经影像、定量感觉测试、血浆 炎症测量、自主神经张力），预测对每个的不同反应 疗法，以及推断治疗的作用机制（n=200）。 通过提供有关 MRC 参与者的数据以及做出贡献，为更广泛的 BACPAC 计划做出贡献 BACPAC 的科学专业知识、研究方法和领导力。

项目成果

Fibromyalgia and centralized pain in the rheumatoid arthritis patient.

类风湿性关节炎患者的纤维肌痛和集中性疼痛。

• 发表时间: 2023-05-01
• 影响因子: 5.1
• 作者: Minhas, Deeba;Murphy, Anne;Clauw, Daniel J
• 通讯作者: Clauw, Daniel J

An Interventional Response Phenotyping Study in Chronic Low Back Pain: Protocol for a Mechanistic Randomized Controlled Trial.

慢性腰痛的介入反应表型研究：机械随机对照试验方案。

• 发表时间: 2023-08-04
• 作者: Hassett, Afton L;Williams, David A;Harris, Richard E;Harte, Steven E;Kaplan, Chelsea M;Schrepf, Andrew;Kratz, Anna L;Brummett, Chad M;Kidwell, Kelley M;Tsodikov, Alexander;Shaikh, Sana;Murphy, Susan L;Lobo, Remy;King, Anthony;Favorite, Todd
• 通讯作者: Favorite, Todd