Genetic testing to Address Renal Disease Disparities Across the U.S. (GUARDD-US) - Administrative Supplement

通过基因检测解决全美肾脏疾病差异问题 (GUARDD-US) - 行政补充

• 批准号: 10620537
• 负责人: Carol R Horowitz
• 金额: $ 28.81万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-27 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620537
• 关键词: APOL1 gene; Address; Administrative Supplement; Adult; African American population; African ancestry; Antihypertensive Agents; Biological; Blood Pressure; Chronic Kidney Failure; Clinical; Clinical Trials; Diagnosis; Enrollment; Genetic Risk; Genomic medicine; Genotype; Health; Healthcare; High Prevalence; Hypertension; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Mental Depression; Pain management; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pilot Projects; Population Heterogeneity; Randomized; Risk; Testing; TimeLine; behavioral outcome; blood pressure control; cost effectiveness; demographics; disease disparity; genetic testing; genetic variant; high risk; hypertension control; improved; patient population; pharmacogenetic testing; prospective; recruit; secondary outcome; social determinants

Project Summary 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. As part of the IGNITE II network, we are implementing two prospective randomized pragmatic genotype-guided clinical trials (GUARDD-US and ADOPT-PGx) to determine the impact of implementing genetic testing on hypertension, depression, and pain therapies. This administrative supplement request is to extend the GUARDD-US recruitment timeline and increase enrollment from our Clinical Group by an additional 200 study participants. GUARDD-US: 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 found in AAs, increase kidney failure risk 10-fold. We propose a genotype-guided trial to 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 5435 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.

项目摘要 基因组医学改变医疗保健和改善健康的希望才能完全实现 发现与不同人群及其临床医生相关并可以使用。作为一部分 IGNITE II网络，我们正在实施两个前瞻性随机实用基因型引导的临床试验 （Guardd-Us和andy-PGX）确定实施基因检测对高血压的影响， 抑郁症和疼痛疗法。这种行政补充要求是扩展Guardd-us 另外200名研究参与者招募时间表并增加了临床组的入学率。 Guardd-US：慢性肾脏疾病（CKD）与高血压有关。非洲血统的人 （AAS）CKD和肾衰竭的风险最高，高血压的患病率最高，最低 血压率（BP）对照。尽管这种差异是由于社会决定因素所致，但祖先有 生物基础和APOL1高风险遗传变异，在AAS中几乎独有，增加了肾脏 故障风险10倍。我们提出了一项基因型引导的试验，以确定早期知识与延迟知识的影响 3个月收缩压（SBP）的阳性APOL1基因分型会导致。该审判旨在招募5435 有或没有CKD的非裔美国人 APOL1基因检测。在那些APOL1负面的人中，我们还将进行一项试点研究以测试影响 SBP的药物遗传学（PGX）测试。次要结果包括CKD患者的6个月SBP， 订购的药物，肾脏诊断和测试患者心理行为结果，成本效益和 PGX引导高血压管理对SBP的影响。 我们预计这项临床试验的成功结果将提供驱动所需的关键证据 跨患者人群的广泛人口统计学实施基因组医学。