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

项目摘要 痛风影响着830万美国成年人。痛风和高尿酸血症与高血压、高血压的进展有关 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(ULT)已显示出临床结果的改善。然而，尽管有这些发现和 关于痛风管理的国家指南建议，对饮食中嘌呤含量的了解很少 在7种慢性病中，痛风药物的依从性是最低的。我们小组开发了一种 皮肤传感器贴片可以检测汗液中的尿酸(UA)。汗水尿酸与血清有很强的相关性 尿酸(SU)水平使其成为经常采样受试者尿酸水平的理想非侵入性方法。我们 假设为痛风患者提供他们餐前和餐后的UA结果将导致更好的饮食和 服药依从性决定。为了更好地了解控制尿酸对痛风和其他代谢的影响 在这种情况下，我们寻求扩大该系统监测的代谢物和营养的范围。我们寻求 延长皮肤贴片的使用时间，包括早餐和晚餐。我们寻求开发一种 友好、易于使用的数据收集和患者报告界面。我们将评估尿液的影响 酸代谢物监测系统(UR AIMS)对痛风和其他代谢临床结果的增强作用 通过对痛风患者进行为期10周的随机试验，无论是服用或停用尿酸盐治疗(4组)。 具体地说，我们将测试UR的使用是否针对患者餐前和餐后尿酸报告结果 在改善血尿酸控制方面，根据SU&lt；6 mg/dL患者的比例来衡量。因为尿酸盐是 与其他代谢途径交织在一起，我们还将评估UR的干预是否会导致 改善血压、血糖和血脂控制。有了详细的(几乎连续的)预期数据 对于尿酸盐和其他代谢物，我们将在痛风发作之前评估代谢物的变化。这些 观察可能导致对痛风爆发前的触发因素有新的理解。除了……之外 嘌呤代谢物，我们将测量别嘌醇(最常见的降尿酸盐药物)代谢物， 奥比嘌醇。在人群水平上还没有实现别嘌醇的有效剂量。产生混乱的原因是 多年来的剂量建议与当前的剂量建议相互冲突(从低开始并滴定 缓慢增加到目标剂量，从而降低SU&lt；6 mg/dL)。此外，肾脏疾病、体型和利尿剂的影响 所有的撞击有效剂量都需要达到SU目标。通过持续的氧嘌醇措施，我们将评估 如果初始稳定的氧嘌醇和尿酸的变化可以预测所需滴定结束时的最终剂量 达到SU&lt；6 mg/dL。这一预测规则将简化未来的别嘌醇给药计划，减少 实验室访问次数和提供商互动次数。

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.