IGNITE Cost Extension - Admin Supplement

IGNITE 成本扩展 - 管理补充

基本信息

批准号：
10820198
负责人：
Larisa Humma Cavallari
金额：
$ 135.18万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10820198
关键词：
APOL1 gene Acute Acute Pain Address Administrative Supplement Adult Adverse effects African American population African ancestry Antidepressive Agents Biological Blood Pressure COVID-19 Chronic Kidney Failure Clinical Clinical Trials Data Disparity Dose Effectiveness Enrollment Ethnic Origin Florida Funding Future Genomic medicine Genomics Genotype Guidelines Health Healthcare High Prevalence Hypertension Kidney Failure Knowledge Manuscripts 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 Publications Race Randomized Risk Safety Selection for Treatments Site Test Result Testing Time Universities Vulnerable Populations blood pressure control chronic pain clinically relevant comparison control cost demographics depressive symptoms economic impact effective therapy genetic testing genetic variant health care service utilization health difference health disparity high risk hypertension control hypertensive improved opioid therapy participant enrollment patient population pharmacogenetic testing primary endpoint primary outcome prospective recruit risk minimization secondary analysis social determinants treatment arm treatment as usual

项目摘要

Project Summary The current administrative supplement request is for a 24-month extension with funding to complete the ongoing IGNITE Network pragmatic clinical trials, GUARDD-US and ADOPT-PGx. The GUARDD-US and ADOPT-PGx, have been underway since July 2020 and February 2021, respectively. These trials will help 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, exclusively 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 clinical 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. A 24-month extension with funding is needed due to unanticipated network-wide delays in launching each trial and shutdowns due to COVID-19. The funding requested in this administrative supplement reflects the trial needs as well as enrollment of 50 additional participants for the Depression Trial to address recruitment shortfalls by other groups and for the costs associated with leading analyses and publication costs for 15 secondary manuscripts.

项目概要当前的行政补充请求是延长 24 个月，并提供资金以完成正在进行的 IGNITE 网络实用临床试验、GUARDD-US 和 ADOPT-PGx。 GUARDD-US 和 ADOPT-PGx，分别自2020年7月和2021年2月开始进行。这些试验将有助于确定影响对高血压、抑郁症和疼痛疗法实施基因检测。 GUARDD-US：慢性肾病疾病（CKD）与高血压有关。非洲血统 (AA) 的人患 CKD 的风险最高和肾衰竭，高血压患病率最高，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，但血统具有生物学基础，并且 APOL1 高风险基因变异仅存在于 AA 中，可使肾衰竭风险增加 10 倍。我们提出了一个基因型- 指导试验以确定早期与延迟了解 APOL1 基因分型阳性结果对 3- 的影响每月收缩压（SBP）。该临床试验旨在招募患有高血压的非裔美国人，或没有 CKD，随机分为立即返回 APOL1 基因检测与延迟返回 APOL1 基因检测。在那些 APOL1 阴性，我们还将进行一项试点研究，以测试药物遗传学 (PGx) 测试对 SBP 的影响。 ADOPT-PGx：疼痛和抑郁是影响很大一部分美国人口的疾病。这急性和慢性疼痛的治疗面临着挑战，因为很难找到有效的治疗方法，同时最大限度地减少疼痛不良反应或阿片类药物成瘾的风险。对于抑郁症，几乎没有临床相关的预测因子成功的治疗，导致许多患者得不到充分的治疗。我们提出一个前瞻性的随机实用基因型指导临床试验，测试基因型指导治疗在三种疾病中的效果患者的情况：急性术后疼痛、慢性疼痛和抑郁。对于每个场景，参与者将与通常的药物治疗选择方法相比，随机接受基因型引导的药物治疗。变化使用标准 PROMIS 量表表示疼痛和抑郁控制的患者报告结果定义主要终点。二次分析包括安全终点、整体健康状况的变化以及经济影响以医疗保健利用率的差异为代表。有资金的 24 个月延期是由于 COVID-19 导致每次试验的启动和关闭都出现了意外的网络范围内的延迟，因此需要这样做。这本行政补充申请中要求的资金反映了试验需求以及另外 50 名患者的注册抑郁症试验的参与者，以解决其他团体的招募不足问题和费用与 15 份二级手稿的主要分析和出版成本相关。

项目成果

期刊论文数量（99）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Implementing personalized medicine: development of a cost-effective customized pharmacogenetics genotyping array.

实施个性化医疗：开发具有成本效益的定制药物遗传学基因分型阵列。

DOI：
发表时间：
2012-10
期刊：
影响因子：
6.7
作者：
Johnson, J A;Burkley, B M;Langaee, T Y;Clare;Klein, T E;Altman, R B
通讯作者：
Altman, R B

Emerging roles for pharmacists in clinical implementation of pharmacogenomics.

药剂师在药物基因组学临床实施中的新作用。

DOI：
发表时间：
2014-10
期刊：
影响因子：
4.1
作者：
Owusu;Weitzel, Kristin W;Hatton, Randy C;Staley, Benjamin J;Ashton, Jennifer;Cooper;Johnson, Julie A
通讯作者：
Johnson, Julie A

Effects of Using Personal Genotype Data on Student Learning and Attitudes in a Pharmacogenomics Course.

在药物基因组学课程中使用个人基因型数据对学生学习和态度的影响。

DOI：
发表时间：
2016-09-25
期刊：
影响因子：
3.3
作者：
Weitzel, Kristin Wiisanen;McDonough, Caitrin W;Elsey, Amanda R;Burkley, Benjamin;Cavallari, Larisa H;Johnson, Julie A
通讯作者：
Johnson, Julie A

Implementation of inpatient models of pharmacogenetics programs.

药物遗传学项目住院模型的实施。

DOI：
发表时间：
2016-12-01
期刊：
影响因子：
0
作者：
Cavallari, Larisa H;Lee, Craig R;Duarte, Julio D;Nutescu, Edith A;Weitzel, Kristin W;Stouffer, George A;Johnson, Julie A
通讯作者：
Johnson, Julie A

The importance of phenoconversion when using the CYP2D6 genotype in clinical practice.

在临床实践中使用 CYP2D6 基因型时表型转化的重要性。