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

皮肤尿酸和代谢物监测可改善痛风患者对药物和饮食治疗的个体反应

• 批准号: 10642949
• 负责人: JOHN D FITZGERALD
• 金额: $ 24.22万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10642949
• 关键词: Adherence; Adult; Affect; Alcohols; Allopurinol; American; Biological Markers; Blood Glucose; Blood Pressure; Body Size; Cardiovascular Diseases; Chronic Disease; Clinical; Confusion; Cutaneous; Data; Data Collection; Diet; Diet Modification; Dietary Intervention; Diuretics; Dose; Dyslipidemias; Feedback; Flare; Friends; Fructose; Future; Glucose; Goals; Gout; Guidelines; Health; Health Expenditures; Home; Hypertension; Hyperuricemia; Individual; Intervention; Isoleucine; Kidney Diseases; Knowledge; Laboratories; Measurement; Measures; Metabolic; Metabolic Pathway; Metabolic syndrome; Metabolism; Methods; Microfluidics; Molecular; Monitor; Morbidity - disease rate; Nutrient; Outcome; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Physical activity; Population; Provider; Purines; Randomized, Controlled Trials; Recommendation; Reporting; Reproducibility; Research; Rheumatology; Role; Sampling; Schedule; Scheme; Serum; Sodium Chloride; Standardization; Sweat test; System; Technology; Testing; Therapeutic Intervention; Time; Titrations; Urate; Uric Acid; Visit; Xanthines; arm; blood lipid; college; community setting; dietary; dietary adherence; flexibility; improved; individual response; medication compliance; non-invasive monitor; primary outcome; prospective; purine metabolism; randomized trial; response; secondary outcome; sensor; skin patch; wearable platform; wearable sensor technology; wireless

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.

项目概要 痛风影响着 830 万美国成年人。痛风和高尿酸血症与高血压、糖尿病进展有关 肾脏疾病、心血管疾病和血脂异常。饮食调整可将 SU 降低 1 mg/dL。尿酸盐 降低疗法（ULT）已证明可以改善临床结果。然而，尽管有这些发现和 国家痛风管理指南建议，膳食嘌呤含量知识匮乏 痛风药物的依从性是 7 种慢性疾病中最低的。我们组开发了一个 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餐前和餐后 UA 结果将导致更好的饮食和 药物依从性决定。更好地了解尿酸控制对痛风和其他代谢的影响 在条件允许的情况下，我们寻求扩大该系统监测代谢物和营养物质的范围。我们力求 延长皮肤贴剂的使用时间，包括早餐和晚餐。我们寻求开发一个 友好、易于使用的数据收集和患者报告界面。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果 这是一项为期 10 周的随机试验，对象是患有痛风的受试者，无论是否接受降尿酸治疗（4 组）。 具体来说，我们将测试使用 UR+AIMS 检测患者餐前和餐后尿酸是否报告结果 根据 SU < 6 mg/dL 的患者比例衡量，血清尿酸控制得到改善。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。具有详细的（几乎连续的）前瞻性数据 关于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 观察可能会导致人们对痛风发作前的触发因素有新的认识。此外 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， 奥昔嘌呤醇。别嘌呤醇的有效剂量尚未在人群水平上实现。混乱产生于 多年来的剂量建议与当前的剂量建议相冲突（低起始剂量和滴定剂量） 缓慢上升至目标剂量，使 SU < 6 mg/dL)。此外，肾脏疾病、体型和利尿剂的影响 所有这些都会影响实现 SU 目标所需的有效剂量。通过连续的奥嘌呤醇测量，我们将评估 如果初始稳定的奥嘌呤醇随着 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的别嘌呤醇给药方案，减少 实验室访问和提供者互动的次数。