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 总体组件 NIH BACPAC倡议旨在“产生有关表型，内型，， 机制，诊断，试验结果和治疗反应能力。 。在慢性下腰痛（CLBP）中。 我们认为，密歇根大学（UM）的小组非常适合领导机械研究 中心（MRC）作为更广泛的BACPAC倡议的一部分，因为我们一直在所有这些线路上工作 超过二十年。我们提出了一个单一的研究项目，该项目将带有CLBP患者并使用 以患者为中心的智能设计研究，以纵向跟随这些人，因为他们尝试了几种不同的 基于证据的疗法，而机械研究被覆盖以提出有关什么的关键推断 治疗将在患者内型中起作用。我们将术语介入反应表型用于 在任何精确的医学计划中描述对表型参与者的需求 做和不响应 - 以后可以将机械不同的疾病内表型联系起来 那些优先应对针对这些机制的疗法的人。 UM的第一个具体目标 BACPAC MRC是在CLBP患者队列中进行介入的反应表型（n = 500）。我们 将使用公认的CLBP患者进行长期务实的试验，他们将接受 已知在CLBP有效的干预措施序列。所有CLBP参与者将在最初的6周收到 基于网络的疼痛的患者自我管理计划。第一个治疗期不是测试机理 假设，而是将回归减少或消除为平均值，以及安慰剂的效果 在随后的随机治疗之前与员工互动。然后是症状的参与者 将参加自适应，顺序多重评估随机试验（SMART）以随机分组 从一个列表中，个人进行两次其他治疗，包括：a）基于正念的列表 认知疗法（MBCT）； b）物理疗法和运动； c）杜洛西汀，d）加巴喷丁和e）自我 管理腔。在研究期间的任何时候，参与者（作为持续护理的一部分）也可能 进行硬膜外立体声或方面关节注射或腰手术。虽然参与者不会 随机接受这些介入疗法，我们可以评估差异的预测因子 响应能力。该提案的第二个具体目的是证明目前可用于临床上的可用 得出的措施可以预测对上述疗法的差异反应（n = 500）。第三个特定 目的是确定新的实验措施（功能性神经影像，定量感觉测试，等离子体 炎症的措施，自主语调）预测对每个的差异反应 疗法以及推断治疗作用机理（n = 200）。第四个具体目的是 通过提供有关MRC参与者的数据以及贡献的数据来为更广泛的BACPAC计划做出贡献 BACPAC的科学专业知识，研究方法和领导力。