Research Project

项目摘要/摘要 研究项目 慢性下腰痛的循证治疗通常包括药理学和非药理学的结合。 和程序性治疗。然而，这些治疗方法对超过一小部分的患者都没有很好的效果， 目前，对于哪些患者应该使用什么治疗方法(即精确度)，几乎没有指导 医学)。针对cLBP的bacpac精准医学计划将试图通过深入的 对cLBP参与者进行表型分析，以确定引起cLBP的各种潜在机制。我们觉得一个 这种表型的关键要素是也要了解哪些参与者对哪些疗法有反应，所以 然后我们可以最终根据cLBP患者的哪些潜在因素选择适当的治疗方法 机制是导致他们疼痛和功能障碍的原因之一。我们在bacpac MRC中的中心假设 研究项目是一项干预反应表型研究可以识别不同疾病的个体 他们疼痛的潜在机制，因此对基于证据的干预措施的反应不同 CLBP“。为了解决这个假设，我们将对cLBP进行一项随机对照的SMART研究， 遵循三个目标。第一个目标是在一组受试者中进行干预反应表型研究 慢性下腰痛患者。我们将使用一组cLBP患者(n=500)进行一项务实的试验，这些患者将接受 已知对慢性下腰痛有效的干预顺序。在为期6周的时间里，所有cLBP参与者都将收到一个网络- 基于疼痛的自我管理计划。六周后，仍有症状的患者将被登记 在一项序贯、多重评估、随机试验(SMART)设计研究中，随机分为一系列 治疗，包括：a)基于正念的认知治疗，b)物理治疗/锻炼，c)穴位按压，d) 度洛西汀，或e)普瑞巴林。12周后，仍然有症状的个人将被重新随机分配到 不同的治疗再延长12周。有了所有参与者的这些信息，我们将覆盖AIMS 2和3，这将确定对每个治疗有反应的参与者的子集。在《目标2》中，我们将展示 目前可用的、临床衍生的测量方法可以预测对上述情况的不同反应 治疗。在目标3中，目标1和目标2中的一部分个体将接受更深的表型分析(n=200)， 确定新的实验指标，预测对上述每种疗法的不同反应，如 以及推断治疗的作用机制。这些深入的表型鉴定访问花费了近一整天的时间 每项研究将在每个治疗期之前和研究完成时进行，并将包括 功能神经成像，定量感觉测试，血浆炎症测量，以及 自主音调。

PROJECT SUMMARY / ABSTRACT RESEARCH PROJECT The evidence-based treatments for cLBP typically include a combination of pharmacologic, non-pharmacologic and procedural treatments. However, none of these treatments works well in more than a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients (i.e. precision medicine). The BACPAC precision medicine initiative for cLBP will attempt to solve this problem by deeply phenotyping cLBP participants to identify the various underlying mechanisms causing cLBP. We feel that a critical element of such phenotyping is to also understand which participants respond to which therapies, so that we can then eventually choose the appropriate treatment for a cLBP patient based on which underlying mechanisms are contributing to their pain and dysfunction. Our central hypothesis in our BACPAC MRC Research Project is that an Interventional Response Phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based interventions for cLBP”. To address this hypothesis, we will conduct a randomized controlled SMART study of cLBP with the following three aims. The first aim is to perform an Interventional Response Phenotyping study in a cohort of cLBP patients. We will perform a pragmatic trial using a cohort of cLBP patients (n=500), who will receive a sequence of interventions known to be effective in cLBP. For 6 weeks, all cLBP participants will receive a web- based self-management program for pain. After six weeks, individuals who remain symptomatic will be enrolled in a Sequential, Multiple Assessment, Randomized Trial (SMART) design study and randomized to a series of treatments, including: a) mindfulness based cognitive therapy, b) physical therapy/exercise, c) acupressure, d) duloxetine, or e) pregabalin. After 12 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 12 weeks. Having this information on all participants, we will overlay Aims 2 and 3, which will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically-derived measures, can predict differential responsiveness to the above therapies. In Aim 3, a subset of the individuals in Aims 1 and 2 will receive deeper phenotyping (n=200), to identify new experimental measures that predict differential responsiveness to each of the above therapies, as well as to infer mechanisms of action of treatments. These deep phenotyping visits take nearly an entire day each, will be performed prior to each treatment period and at the completion of the study, and will include functional neuroimaging, quantitative sensory testing, plasma measures of inflammation, and measures of autonomic tone.