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直到 这些发现变得与不同的人群及其临床医生相关并可供其使用。作为该计划的一部分 IGNITE II网络，我们正在实施两项前瞻性、随机、实用、基因型指导的临床试验 (GUARDD-US和采用-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。这项行政补充请求是为了延长GUARDD-US 招募时间表，并增加我们临床组的额外200名研究参与者。 GUARDD-US：慢性肾脏疾病(CKD)与高血压有关。具有非洲血统的人 (AAS)患CKD和肾衰竭的风险最高，高血压患病率最高，而 血压控制率。虽然这种差异在一定程度上是由社会决定因素造成的，但祖先 在AAs中几乎独有的生物学基础和APOL1高危基因变异可增加肾脏 失败的风险是原来的10倍。我们建议进行一项以基因型为导向的试验来确定早期知识与延迟知识的效果。 在3个月的收缩压(SBP)中APOL1基因分型阳性的结果。该试验的目标是招募5435人 患有高血压的非裔美国人，有或没有CKD，随机分为即刻和延迟恢复组 APOL1基因检测。对于那些APOL1阴性的人，我们还将进行一项试点研究，以测试其影响 对SBP进行药物遗传学(PGx)检测。次要结果包括CKD患者6个月的SBP， 订购药物，肾脏诊断和测试患者的心理行为结果，成本效益，以及 前列腺素X引导下的高血压治疗对SBP的影响 我们预计这项临床试验的成功结果将提供推动 在广泛的患者群体中实施基因组医学。

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.