Research Project

项目总结/摘要 研究项目 cLBP的循证治疗通常包括药理学、非药理学和免疫学的组合。 和程序性治疗。然而，这些治疗方法中没有一种在一小部分患者中效果良好， 并且目前关于在哪些患者中应该使用什么治疗的指导很少（即精确性 医学）。针对cLBP的BACPAC精准医学计划将试图通过深入研究来解决这一问题。 对cLBP参与者进行表型分型以鉴定引起cLBP的各种潜在机制。我们觉得 这种表型分析的关键要素是了解哪些参与者对哪些治疗有反应， 我们最终可以根据患者的基础疾病选择合适的治疗方法， 导致了他们的疼痛和功能障碍我们在BACPAC MRC中的中心假设 研究项目是，干预反应表型研究可以识别不同的个体 因此，他们对基于证据的干预措施的反应不同， cLBP”。为了解决这一假设，我们将进行一项随机对照的SMART研究cLBP与 三个目标。第一个目的是在一个队列中进行干预反应表型研究， cLBP患者我们将使用cLBP患者队列（n=500）进行一项实用性试验，这些患者将接受 已知对cLBP有效的干预序列。为期6周，所有cLBP参与者将收到一个网络- 疼痛的自我管理计划。六周后，仍有症状的个体将入组 在一项序贯、多重评估、随机试验（SMART）设计研究中， 治疗，包括：a）基于正念的认知疗法，B）物理疗法/锻炼，c）穴位按摩，d） 度洛沙坦，或e）普瑞巴林。12周后，仍有症状的个体将被重新随机分配至 另外12周的不同治疗。有了所有参与者的这些信息，我们将覆盖目标 2和3，这将确定对每种治疗有反应的参与者子集。在目标2中，我们将展示 目前可用的临床衍生措施可以预测对上述药物的不同反应性 治疗在目标3中，目标1和目标2中的个体的子集将接受更深的表型分型（n=200），以 确定新的实验措施，预测对上述每种治疗的不同反应， 以及推断治疗的作用机制。这些深入的表型分析访问需要将近一整天的时间 将在每个治疗期之前和研究完成时进行，包括 功能性神经成像、定量感觉测试、炎症的血浆测量和 自主神经张力

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.