Implementing genomic medicine through pragmatic trials in diverse and underserved populations across Indiana.

通过在印第安纳州不同且服务不足的人群中进行实用试验来实施基因组医学。

• 批准号: 10561225
• 负责人: Paul Dexter
• 金额: $ 16.64万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10561225
• 关键词: APOL1 gene; Adult; Affect; African American population; African ancestry; Antihypertensive Agents; Behavior; Biological; Blood Pressure; Chronic Kidney Failure; Clinical; Clinical Trials; Diagnosis; Genetic Risk; Genomic medicine; Genotype; Health; Healthcare; High Prevalence; Hypertension; Indiana; Individual; Kidney; Kidney Failure; Knowledge; Patient-Focused Outcomes; Patients; Persons; Pharmaceutical Preparations; Pharmacogenomics; Pilot Projects; Population; Population Heterogeneity; Provider; Randomized; Risk; Testing; Underserved Population; behavioral outcome; blood pressure control; cost effective; cost effectiveness; demographics; genetic information; genetic testing; genetic variant; high risk; hypertension control; improved; patient population; pharmacogenetic testing; pragmatic trial; prospective; recruit; secondary outcome; social determinants

The promise of genomic medicine to transform healthcare and improve health will not be fully realized until discoveries become relevant to and available for use by diverse populations and their clinicians. Chronic kidney disease (CKD) is associated with hypertension. People with African ancestry (AAs) have the highest risk of CKD and kidney failure, the highest prevalence of hypertension, and the lowest rate of blood pressure (BP) control. While this disparity is in part due to social determinants, ancestry has biological underpinnings and APOL1 high-risk genetic variants, nearly exclusive in AAs, increase kidney failure risk 10-fold. As part of the IGNITE II network, we will continue to conduct the prospective randomized pragmatic genotype-guided clinical trial, GUARDD-US, to determine the impact of implementing APOL1 and antihypertensive pharmacogenomic testing on hypertension control. The trial will determine the effect of early vs. delayed knowledge of a positive APOL1 genotyping result on 3-month systolic blood pressure (SBP). The trial aims to recruit African Americans with hypertension, with or without CKD, randomized to immediate versus delayed return of APOL1 genetic testing. In those who are APOL1 negative, we will also conduct a pilot study to test the impact of pharmacogenetic (PGx) testing on SBP. Secondary outcomes include 6-month SBP, in CKD patients, on medications ordered, renal diagnosis and testing patient psycho-behavioral outcomes, cost effectiveness, and the effect of PGX guided hypertension management on SBP. We expect the successful results from this clinical trial will provide critical evidence needed to drive the implementation of genomic medicine across broad demographics of patient populations.

直到基因组医学改变医疗保健和改善健康的承诺才能完全实现 发现与不同人群及其临床医生相关并可供使用。慢性的 肾脏疾病（CKD）与高血压有关。有非洲血统的人 (AA) 拥有最高的 CKD 和肾衰竭的风险、高血压患病率最高、血压发生率最低 （血压）控制。虽然这种差异部分是由于社会决定因素造成的，但血统具有生物学基础 APOL1 高风险基因变异（几乎仅出现在 AA 中）会使肾衰竭风险增加 10 倍。作为一部分 在IGNITE II网络中，我们将继续进行前瞻性随机务实基因型指导 临床试验 GUARDD-US，以确定实施 APOL1 和抗高血压药物的影响 高血压控制的药物基因组学测试。该试验将确定早期与延迟的效果 了解 3 个月收缩压 (SBP) 的 APOL1 基因分型结果呈阳性。该试验旨在 招募患有高血压（无论是否患有 CKD）的非裔美国人，随机分为立即组和延迟组 APOL1 基因检测回归。对于 APOL1 阴性的患者，我们还将进行一项试点研究来测试 药物遗传学 (PGx) 测试对 SBP 的影响。次要结局包括 CKD 患者的 6 个月 SBP 患者、所订购的药物、肾脏诊断和测试、患者心理行为结果、费用 PGX 指导高血压管理对 SBP 的有效性和影响。我们期待成功 该临床试验的结果将为推动基因组学的实施提供所需的关键证据 涵盖广泛的患者群体的医学。