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

项目摘要 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。的一部分 IGNITE II网络，我们正在实施两项前瞻性随机实用基因型指导临床试验 （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。这一行政补充请求是为了延长美国警卫队 招募时间轴，并从我们的临床组增加200名研究参与者。 GUARDD-US：慢性肾脏病（CKD）与高血压相关。非洲裔 (AAs)CKD和肾衰竭的风险最高，高血压的患病率最高， 血压（BP）控制率。虽然这种差异部分是由于社会决定因素，但血统 生物学基础和APOL 1高风险遗传变异，几乎只在AA中发现， 失败风险10倍。我们提出了一个基因型指导的试验，以确定早期与延迟知识的影响 3个月收缩压（SBP）的阳性APOL 1基因分型结果。该试验旨在招募5435名 患有高血压（伴或不伴CKD）的非裔美国人，随机分配至立即与延迟恢复治疗组 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，以测试其影响 SBP的药物遗传学（PGx）检测。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心理行为结果，成本效益，以及 PGX指导下的高血压管理对SBP的影响。 我们预计，这项临床试验的成功结果将为推动 在广泛的患者人群中实施基因组医学。

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.