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.

项目概要 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。作为 IGNITE II网络，我们正在实施两项前瞻性随机实用基因型引导的临床试验 （GUARDD-US 和 ADOPT-PGx）以确定实施基因检测对高血压的影响， 抑郁症和疼痛疗法。此行政补充请求旨在延长 GUARDD-US 招募时间表，并增加我们临床组的 200 名研究参与者。 GUARDD-US：慢性肾脏病 (CKD) 与高血压有关。有非洲血统的人 (AA) 患 CKD 和肾衰竭的风险最高，高血压患病率最高，且患病率最低 血压（BP）控制率。虽然这种差异部分是由于社会决定因素造成的，但血统已经 生物基础和 APOL1 高风险遗传变异（几乎仅在 AA 中发现）可增加肾脏功能 失败风险增加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效果 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5435名 患有高血压（无论是否患有 CKD）的非裔美国人被随机分为立即回归和延迟回归 APOL1 基因检测。对于 APOL1 阴性的人，我们还将进行一项试点研究来测试其影响 SBP 的药物遗传学 (PGx) 测试。次要结局包括 CKD 患者的 6 个月 SBP、 订购的药物、肾脏诊断和测试患者的心理行为结果、成本效益以及 PGX指导高血压管理对SBP的影响。 我们预计这项临床试验的成功结果将为推动这一进程提供关键证据。 在广泛的患者群体中实施基因组医学。