University of Michigan BACPAC Mechanistic Research Center

密歇根大学BACPAC机理研究中心

• 批准号: 9898106
• 负责人: Daniel J Clauw
• 金额: $ 896.94万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898106
• 关键词: Acupressure; Address; Algorithms; American; Back; Biological Markers; Caring; Chronic low back pain; Clinical; Coin; Data; Diagnostic Trial; Diagnostic tests; Disease; Economic Factors; Enrollment; Facet joint structure; Fibromyalgia; Focus Groups; Image; Individual; Inflammation; Injections; Intervention; Knowledge; Lead; Leadership; Left; Light; Link; Measures; Michigan; National Institute of Diabetes and Digestive and Kidney Diseases; Online Systems; Operative Surgical Procedures; Outcome; Pain; Pain Clinics; Pain management; Participant; Patient Outcomes Assessments; Patients; Pelvis; Pharmaceutical Preparations; Phenotype; Physical Examination; Physical therapy exercises; Placebo Effect; Plasma; Positioning Attribute; Precision Medicine Initiative; Procedures; Questionnaires; Randomized; Research; Research Design; Research Methodology; Research Project Grants; Self Administration; Sensory; Spinal; Spine surgery; Steroids; Structure; Surveys; Systems Biology; Testing; Therapeutic; Therapeutic Intervention; Translational Research; United States National Institutes of Health; Universities; Vision; Work; actigraphy; base; chronic pelvic pain; cohort; design; duloxetine; endophenotype; evidence base; experience; gabapentin; individual patient; member; mindfulness based cognitive therapy; mindfulness-based stress reduction; neuroimaging; non-opioid analgesic; nondrug therapy; pain patient; personalized medicine; pragmatic trial; precision medicine; predicting response; psychologic; racial and ethnic; randomized trial; response; self-management program; social; targeted treatment; treatment duration; treatment response; working group

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.

项目摘要/摘要 整体组件 NIH bacpac计划旨在“产生关于表型、内型、 机制、诊断、试验结果和治疗反应。。。慢性下腰痛(CLBP)。 我们认为我们密歇根大学(UM)的团队非常适合领导一项力学研究 中心(MRC)作为更广泛的BACPAC倡议的一部分，因为我们一直在沿着所有这些路线工作 已经有二十多年了。我们提出了一个单一的研究项目，该项目将接受慢性下腰痛患者并使用 以患者为中心的智能设计研究，纵向跟踪这些人尝试几种不同的 循证治疗，而机械研究被覆盖以得出关于什么的关键推断 治疗将根据患者的内型而起作用。我们使用术语介入反应表型来 描述在任何精确医学计划中需要让参与者了解他们所使用的治疗方法 做和不做反应-这样人们以后就可以将机械上不同的疾病内表型与 那些对针对这些机制的治疗有优先反应的人。UM的第一个具体目标 Bacpac MRC将在一组cLBP患者(n=500)中进行介入性反应表型分析。我们 将使用一组公认的cLBP患者进行长期务实试验，这些患者将获得 已知对慢性下腰痛有效的干预顺序。所有cLBP参与者将在前6周收到 一个基于网络的疼痛患者自我管理程序。这第一个治疗期并不是在测试机械性 假设，但相反将减少或消除回归到平均值以及安慰剂效应 在随后的随机治疗之前，与工作人员互动。然后仍有症状的参与者 将参加自适应序贯多项评估随机试验(SMART)以随机化 每个人接受两种额外的治疗，每种治疗为期12周，清单包括：a)基于正念的治疗 认知疗法(MBCT)；b)物理治疗和锻炼；c)度洛西汀，d)加巴喷丁和e)自我 按压穴位。在研究过程中的任何时候，参与者(作为持续护理的一部分)还可以 接受硬膜外类固醇或小关节注射，或腰椎手术。尽管参与者将不会 随机接受这些介入治疗，我们可以评估不同的预测因素 响应性。这项建议的第二个具体目标是证明目前在临床上可用的- 衍生测量可以预测对上述疗法的不同反应(n=500)。第三个具体问题 目的是确定新的实验方法(功能神经成像、定量感觉测试、血浆 炎症测量，自主神经音调)，预测对每一种 治疗，以及推断治疗的作用机制(n=200)。第四个具体目标是 通过提供我们MRC参与者的数据以及为更广泛的BACPAC计划做出贡献 BACPAC的科学专长、研究方法和领导。