Mechanistic-Based Treatment of Interstitial Cystitis/Bladder Pain Syndrome

摘要： 间质性膀胱炎/膀胱疼痛综合征 (IC/BPS) 是一种使人衰弱的慢性疾病，其特征是疼痛、 压力和骨盆区域不适以及泌尿系统症状。 IC/BPS 所涉及的疼痛可以 使人衰弱且无法治愈。就目前情况而言，许多针对 IC/BPS 的可用治疗方法缺乏有力的证据 它们的使用对患者来说成本高昂。此外，患者对医疗护理表示严重不满， 将治疗描述为“反复试验”、昂贵且有“支离破碎”的治疗计划可供遵循。 由于缺乏对病情的清晰了解，IC/BPS 的治疗进展已经停滞，因为症状 和演示文稿差异很大。由于这些原因，国家组织优先考虑改进的需要 治疗选择和对 IC/BPS 的理解。领先的多机构研究网络现已 发现患有 IC/BPS 的个体具有不同的亚组或“表型”，其主要特征是 疼痛分布于全身。 IC/BPS 的这些表现具有独特的临床和 神经生物学特征。具体来说，虽然一部分 IC/BPS 患者的症状主要表现在 骨盆区域（“周围”表型），其他人会经历骨盆以外的额外疼痛，并伴有 睡眠不佳、认知功能障碍、情绪困扰和能量消耗（“集中”表型）。 在神经生物学特征方面，具有“集中化”表现的个体也表现出夸张的表现 对离体刺激的炎症反应和对诱发疼痛的增强反应。由我们的支持 初步证据，该项目的总体目标是评估 IC/BPS 表型如何影响反应 通常不考虑患者表型而给予两种不同的治疗：盆底物理治疗 (PT) 和 针对 IC/BPS 的认知行为疗法 (CBT)。我们假设我们可以预测那些会做出反应的人 根据报告的身体疼痛分布（主要是骨盆疼痛，疼痛 骨盆外）。我们正在提议一项随机机制试验来评估哪些参与者可能 从每种治疗中获益（目标 1）并评估神经生物学机制是否可以调节 结果和治疗带来的变化（目标 2）。根据个人报告的基线广泛疼痛水平， 我们将随机分配 220 名参与者接受 8 周的 CBT 或 10 周的 PT。参与者将 在整个过程中（6 个月前、6 个月后和 6 个月时）接受三项评估。评估包括患者报告 结果、炎症的生物标志物和心理物理测试[在每个时间点进行]。这个 该项目在定制治疗和改善未来 IC/BPS 精准医疗护理工作方面具有巨大潜力。

ABSTRACT: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic condition characterized by pain, pressure, and discomfort in the pelvic region coupled with urinary symptoms. The pain involved in IC/BPS can be debilitating and is incurable. As it stands, many of the available treatments for IC/BPS lack strong evidence for their use and are costly to patients. Further, patients report significant dissatisfaction with medical care, describing treatments as “trial-and-error," expensive, and having “fragmented” treatment plans to follow. Treatment advances in IC/BPS have stalled due to a lack of clear understanding of the condition, as symptoms and presentations vary widely. For these reasons, national organizations have prioritized the need to improve both treatment options and understanding of IC/BPS. Leading multi-institutional research networks have now identified that individuals with IC/BPS have distinct subgroups, or “phenotypes,” largely characterized by the distribution of pain throughout the body. These presentations of IC/BPS have distinct clinical and neurobiological features. Specifically, while a proportion of individuals with IC/BPS have symptoms primarily in the pelvic region (“peripheral” phenotype), others experience additional pain outside of the pelvis coupled with unrefreshing sleep, cognitive dysfunction, emotional distress, and energy depletion (“centralized” phenotype). In terms of neurobiological features, individuals with “centralized” presentations also exhibit exaggerated inflammatory responses to ex vivo stimulation and heightened responses to evoked pain. Supported by our preliminary evidence, the overall goal of this project is to assess how IC/BPS phenotype may affect response to two different therapies often given without regard to patient phenotype, pelvic floor physical therapy (PT) and cognitive-behavioral therapy (CBT) for IC/BPS. We hypothesize that we can predict those who will respond preferentially to either form of treatment based on reported bodily pain distribution (pelvic pain primarily, pain outside of the pelvis). We are proposing a randomized mechanistic trial to evaluate which participants may benefit from each treatment (Aim 1) and evaluate whether neurobiological mechanisms may moderate outcomes and change with treatment (Aim 2). Per an individual’s reported level of baseline widespread pain, we will randomize 220 participants to receive either 8-weeks of CBT or 10-weeks of PT. Participants will receive three assessments throughout, [before, after, and at 6- months]. Assessments include patient-reported outcomes, biological markers of inflammation, and psychophysical testing [taken at each timepoint]. This project has great potential to tailor treatment and improve future IC/BPS precision-medicine care efforts.