Cutaneous uric acid and metabolite monitoring to improve individual response to pharmaceutical and dietary treatment in patients with gout

项目摘要 痛风影响了830万美国成年人。痛风和高尿酸血症与高血压， 肾脏疾病、心血管疾病和血脂异常。饮食调整可使SU降低1 mg/dL。尿酸盐 降低治疗（lowering therapy，LDT）已证明临床结果的改善。然而，尽管这些发现和 痛风管理的国家指南建议，关于饮食嘌呤含量的知识很少 痛风药物的依从性在7种慢性病中最低。我们的团队开发了一个 皮肤传感器贴片，可以检测汗液中的尿酸（UA）。汗液UA与血清UA有较强的相关性 尿酸盐（SU）水平，使其成为一种理想的非侵入性方法，经常采样对象的尿酸水平。我们 假设为痛风患者提供餐前和餐后UA结果将导致更好的饮食和 药物依从性决定。为了更好地了解尿酸盐控制对痛风和其他代谢的影响， 在特定条件下，我们寻求扩大该系统监测的代谢物和营养物质的范围。我们寻求 延长皮肤贴剂的使用时间，包括早餐和晚餐。我们致力发展一个 用于数据收集和患者报告的友好、易于使用的界面。我们将评估URIC的影响 AcId +代谢物监测系统（UR+AIMS）增强痛风和其他代谢临床结局 通过一项为期10周的随机试验，对痛风患者进行降尿酸治疗或停药（4组）。 具体而言，我们将测试UR+AIMS与患者餐前和餐后尿酸报告结果的使用是否 通过测量SU < 6 mg/dL的患者比例，改善血清尿酸盐控制。由于尿酸盐是 与其他代谢途径交织在一起，我们还将评估UR+AIMS干预是否会导致 改善血压、血糖和血脂控制。详细（几乎连续）的前瞻性数据 尿酸盐和其他代谢物，我们将评估痛风发作前代谢物的变化。这些 观察可能导致对痛风发作前的触发因素的新理解。除了 嘌呤代谢物，我们将测量别嘌呤醇（最常见的降尿酸药物）代谢物， 羟嘌呤醇。别嘌呤醇的有效剂量尚未达到人口水平。困惑源于 多年来的给药建议和当前的给药建议（从低剂量开始， 缓慢上升至降低SU < 6 mg/dL的目标剂量）。此外，肾脏疾病、体型和利尿剂的影响 所有影响达到SU目标所需的有效剂量。通过持续的奥昔嘌呤醇测量，我们将评估 如果初始稳定的羟嘌呤醇沿着UA的变化可以预测滴定结束时所需的最终剂量 达到SU < 6 mg/dL。该预测规则将简化未来别嘌呤醇给药方案， 实验室访问和提供者互动的次数。

Project Summary Gout affects 8.3 million of US adults. Gout and hyperuricemia are associated with hypertension, progression of renal disease, cardiovascular disease, and dyslipidemia. Dietary modifications can lower SU by 1 mg/dL. Urate lowering therapy (ULT) has demonstrated improvement in clinical outcomes. Yet despite these findings and national guideline recommendations for the management of gout, knowledge about dietary purine content is poor and adherence with gout medications is the lowest among 7 chronic diseases. Our group has developed a cutaneous sensor patch that can detect uric acid (UA) in sweat. Sweat UA has strong correlation with serum urate (SU) levels making it an ideal non-invasive method to frequently sample subject’s uric acid levels. We postulate that providing patients with gout their pre- and post-prandial UA results will result in better dietary and medication adherence decisions. To better understand the impact of urate control on gout and other metabolic conditions, we seek to expand the breadth of metabolites and nutrients monitored by this system. We seek to extend the duration of use for the skin patch to include morning and evening meals. We seek to develop a friendly, easy to use interface for data collection and patient reports. We will evaluate the impact of the URic AcId + metabolite Monitoring System (UR+AIMS) enhancements on gout and other metabolic clinical outcomes though a 10-week randomized trial for subjects with gout either on or off urate lowering treatments (4 arms). Specifically, we will test whether the use of UR+AIMS with patient pre- and post-prandial uric acid reports results in improved serum urate control as measured by proportion of patients with SU < 6 mg/dL. Since urate is intertwined with other metabolic pathways, we will also evaluate whether UR+AIMS intervention results in improved blood pressure, blood sugar and lipid control. With the detailed (almost continuous) prospective data on urate and other metabolites, we will evaluate the changes in metabolites prior to a gout flare. These observations may lead to new understanding about the triggering factors preceding a gout flare. In addition to purine metabolites, we will be measuring the allopurinol (most common urate lowering medication) metabolite, oxypurinol. Effective dosing of allopurinol has not been achieved at population level. Confusion arises from conflicting dosing recommendations over the years and current dosing recommendations (start low and titrate up slowly to target dose that lowers SU < 6 mg/dL). Furthermore, impact of renal disease, body size and diuretics that all impact effective dose needed to achieve SU goal. With continuous oxypurinol measures, we will evaluate if the initial steady oxypurinol along with change in UA can predict the ultimate dose at the end of titration required to achieve SU < 6 mg/dL. This prediction rule would simplify future allopurinol dosing schedules, reducing the number of lab visits and provider interactions.