Sparking Advancements in Genomic Medicine

激发基因组医学的进步

• 批准号: 10629549
• 负责人: Larisa Humma Cavallari
• 金额: $ 75.04万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-16 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629549
• 关键词: APOL1 gene; Acute; Acute Pain; Administrative Supplement; Adult; Adverse effects; African American population; African ancestry; Antidepressive Agents; Biological; Blood Pressure; Budgets; COVID-19; Chronic Kidney Failure; Clinical; Clinical Trials; Data; Dose; Effectiveness; Enrollment; Florida; Future; Genomic medicine; Genomics; Genotype; Goals; Guidelines; Health; Healthcare; High Prevalence; Hypertension; Kidney Failure; Knowledge; Mental Depression; Opiate Addiction; Opioid; Outcome; Pain; Pain management; Participant; Patient Outcomes Assessments; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pharmacotherapy; Pilot Projects; Population; Population Heterogeneity; Postoperative Pain; Pragmatic clinical trial; Provider; Randomized; Risk; Safety; Selection for Treatments; Site; Test Result; Testing; Universities; Vulnerable Populations; base; blood pressure control; chronic pain; clinically relevant; demographics; depressive symptoms; economic impact; effective therapy; genetic testing; genetic variant; health care service utilization; health disparity; high risk; hypertension control; hypertensive; improved; opioid therapy; patient population; pharmacogenetic testing; primary endpoint; primary outcome; prospective; racial and ethnic; recruit; risk minimization; secondary analysis; social determinants; treatment arm; treatment as usual

Project Summary As part of the IGNITE II network, two prospective randomized pragmatic genotype-guided clinical trials, GUARDD-US and ADOPT-PGx, have been underway since July 2019 and February 2021, respectively. These trials will help to determine the impact of implementing genetic testing on hypertension, depression, and pain therapies. 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 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. ADOPT-PGx: Pain and depression are conditions that impact substantial proportions of the US population. The treatment of acute and chronic pain is challenged by the difficulty of finding effective therapies while minimizing the risk of adverse effects or opioid addiction. For depression, there are few clinically relevant predictors of successful treatment, which results in inadequate therapy for many patients. We propose a prospective randomized pragmatic genotype-guided clinical trial that tests the effect of genotype-guided therapy in three scenarios of patients: acute post-surgical pain, chronic pain, and depression. For each scenario, participants will be randomized to genotype-guided drug therapy versus usual approaches to drug therapy selection. Changes in patient reported outcomes representing pain and depression control using standard PROMIS scales define the primary endpoints. Secondary analyses include safety endpoints, changes in overall well-being, and economic impact represented by differences in healthcare utilization. The current administrative supplement request reflects trial needs for Year 5/9 largely due to unanticipated network-wide delays with the ADOPT-PGx and GUARDD-US trials and shutdowns due to COVID-19. In addition, this administrative request reflects the UF Clinical Group’s (CG) enrollment of 100 additional participants for the Acute Pain Trial, bringing UF’s enrollment goal to 850 participants.

项目概要 作为 IGNITE II 网络的一部分，两项前瞻性随机实用基因型指导临床试验， GUARDD-US 和 ADOPT-PGx 分别自 2019 年 7 月和 2021 年 2 月开始进行。这些 试验将有助于确定基因检测对高血压、抑郁症和疼痛的影响 疗法。 GUARDD-US：慢性肾脏病 (CKD) 与高血压有关。非洲人 血统 (AA) 患 CKD 和肾衰竭的风险最高，高血压患病率最高，并且 血压（BP）控制率最低。虽然这种差异部分是由于社会决定因素造成的， 血统具有生物学基础和 APOL1 高风险遗传变异，几乎只在 AA 中发现， 肾衰竭风险增加 10 倍。我们提出了一项基因型引导的试验，以确定早期与后期的效果。 延迟得知 3 个月收缩压 (SBP) 的 APOL1 基因分型阳性结果。审判 旨在招募患有高血压（无论是否患有 CKD）的非裔美国人，随机分为立即组和 APOL1 基因检测延迟返回。对于 APOL1 阴性的患者，我们还将进行试点研究 测试药物遗传学 (PGx) 测试对 SBP 的影响。 ADOPT-PGx：疼痛和抑郁是病症 这影响了相当大比例的美国人口。急慢性疼痛的治疗面临挑战 由于难以找到有效的治疗方法，同时最大限度地降低不良反应或阿片类药物成瘾的风险。为了 对于抑郁症，成功治疗的临床相关预测因素很少，这导致治疗效果不充分 为许多患者提供治疗。我们提出了一项前瞻性随机实用基因型指导的临床试验 测试基因型引导治疗在三种情况下患者的效果：急性术后疼痛、慢性疼痛 疼痛和抑郁。对于每种情况，参与者将被随机分配接受基因型引导的药物治疗 与通常的药物治疗选择方法相比。患者报告的代表疼痛的结果的变化 使用标准 PROMIS 量表的抑郁控制定义了主要终点。二次分析 包括安全终点、整体福祉的变化以及以差异为代表的经济影响 医疗保健利用。目前的行政补充请求主要反映了5/9年级的审判需求 由于 ADOPT-PGx 和 GUARDD-US 试验出现意外的全网延迟以及由于以下原因而关闭 新冠肺炎。此外，这一行政要求反映了 UF 临床小组 (CG) 的注册人数为 100 急性疼痛试验的额外参与者，使佛罗里达大学的注册目标达到 850 名参与者。