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.

基因组医学改变医疗保健和改善健康的承诺将不会完全实现， 发现变得与不同人群及其临床医生相关并可供其使用。慢性 肾病（CKD）与高血压有关。非洲血统的人（AAs）拥有最高的 CKD和肾衰竭的风险，高血压的患病率最高，血压的患病率最低 (BP)控制虽然这种差异部分是由社会决定因素造成的，但祖先有生物学基础 而APOL 1高风险遗传变异，几乎只存在于AA中，使肾衰竭风险增加10倍。的一部分 IGNITE II网络，我们将继续进行前瞻性随机实用基因型指导 临床试验GUARDD-US，以确定实施APOL 1和抗高血压药物的影响 药物基因组学测试对高血压控制的影响。该试验将确定早期与延迟的效果 3个月收缩压（SBP）APOL 1基因分型结果阳性的知识。该试验旨在 招募患有高血压（伴或不伴CKD）的非裔美国人，随机分为即刻组和延迟组 APOL 1基因检测对于APOL 1阴性的患者，我们还将进行一项试点研究， 药物遗传学（PGx）检测对SBP的影响。次要结局包括CKD患者的6个月SBP 患者，按医嘱用药，肾脏诊断和检测患者心理行为结局，费用 有效性，以及PGX指导的高血压管理对SBP的影响。我们期待成功的 这项临床试验的结果将为推动基因组治疗的实施提供关键证据。 在广泛的患者人群中使用药物。