Sparking Advancements in Genomic Medicine

激发基因组医学的进步

• 批准号: 10553452
• 负责人: Larisa Humma Cavallari
• 金额: $ 62.33万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553452
• 关键词: APOL1 gene; Administrative Supplement; African American population; African ancestry; Age-Years; Alabama; Blood Pressure; Chronic Kidney Failure; Clinical; Clinical Trials; Enrollment; Ensure; Florida; Genetic Risk; Genomic medicine; Genotype; Hypertension; Kidney Diseases; Kidney Failure; Knowledge; Participant; Persons; Pilot Projects; Prevalence; Randomized; Research; Sample Size; Site; Testing; Universities; disease disparity; genetic testing; high risk; improved; member; pharmacogenetic testing; power analysis; primary outcome; prospective; recruit; risk variant

Project Summary As part of the IGNITE II network, the Genetic testing to Understand Renal Disease Disparities in the U.S. (GUARDD-US) clinical trial has been underway since July 2019. GUARDD-US is a prospective randomized pragmatic genotype-guided clinical trial aimed at determining the effect of early vs. delayed knowledge of a positive APOL1 genotyping result on 3- month systolic blood pressure (SBP). African Americans between 18 and 70 years of age with hypertension, with or without chronic kidney disease (CKD) are recruited and randomized to immediate versus delayed return of APOL1 genetic testing. In those who are APOL1 negative, a pilot study to test the impact of pharmacogenetic (PGx) testing on SBP is also underway. The current administrative supplement request reflects a planned increase in enrollment for the GUARDD-US trial. Because the observed prevalence the actionable APOL1 high-risk genotype is significantly lower than projected in the initial sample size calculations (current 14.6% versus 17%), an increase in sample size from 5,435 to 6,600 is required to ensure adequate power for analysis of the primary outcome. In addition, some sites have been unable to meet their recruitment targets, and it is not anticipated that they will make up the shortfall expeditiously. The University of Florida (UF) Clinical Group will support the GUARDD-US increased enrollment request by increasing its enrollment target by 40% (to 700 from 500 participants) and has agreed to add the University of Alabama at Birmingham as a member of its Clinical Group to enroll an additional 300 research participants into the trial.

项目概要 作为 IGNITE II 网络的一部分，了解美国肾脏疾病差异的基因检测 (GUARDD-US) 临床试验自 2019 年 7 月开始进行。GUARDD-US 是一项前瞻性、随机、实用基因型指导的临床试验 临床试验旨在确定早期与延迟了解 APOL1 基因分型阳性结果对 3- 每月收缩压（SBP）。 18 至 70 岁之间患有高血压（无论有或没有）的非裔美国人 招募慢性肾病 (CKD) 患者并随机分为立即返回 APOL1 基因检测和延迟返回 APOL1 基因检测。 对于 APOL1 阴性的患者，还开展了一项试点研究，以测试药物遗传学 (PGx) 测试对 SBP 的影响 进行。当前的行政补充请求反映了 GUARDD-US 招生计划的增加 审判。由于观察到的可采取行动的 APOL1 高风险基因型的患病率明显低于预测的患病率 初始样本量计算（当前 14.6% 对比 17%），需要将样本量从 5,435 增加到 6,600 确保有足够的能力来分析主要结果。此外，一些网站已经无法满足他们的要求 招聘目标，预计他们不会迅速弥补缺口。佛罗里达大学 (UF) 临床小组将通过将其注册目标增加 40%（从 500 名参与者增加到 700 名）并同意将阿拉巴马大学伯明翰分校作为其成员 临床小组将另外招募 300 名研究参与者参加试验。