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