TOXICOGENOMICS OF ACETAMINOPHEN HEPATOTOXICITY- RECHALLENGE PROTOCOL

对乙酰氨基酚肝毒性的毒理学 - 再攻击方案

• 批准号: 7716907
• 负责人: PAUL B WATKINS
• 金额: $ 5.43万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-02 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716907
• 关键词: Acetaminophen; Admission activity; Blood specimen; Computer Retrieval of Information on Scientific Projects Database; Data; Dose; Enzymes; Female; Funding; Gene Expression; Gene Expression Profile; Grant; Hepatotoxicity; Home environment; Institution; Liver; Monitor; Outcome; Participant; Physiological; Plasma; Procedures; Protocols documentation; Purpose; Research; Research Personnel; Resources; Safety; Serum; Source; Toxicogenomics; United States National Institutes of Health; Urine; Visit; Week; Woman; day; healthy volunteer; interest; male; men; metabolomics; peripheral blood; response; transcriptomics

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Purpose: In this study, N=10 eligible normal healthy volunteers (5 men, 5 women) who have not been exposed to acetaminophen in the past six months will be admitted to the GCRC and challenged with acetaminophen (APAP: 1g Q6H for 10days). Then after avoiding APAP at home for two weeks these subjects will be re-admitted and re-challenged (1g Q6H for 10days). The outcomes of interest during each 10-day challenge are the maximum observed changes from baseline for the following responses: (1) serum log10ALT and other related liver enzymes, (2) gene expression indicated by peripheral blood transcriptome, (3) plasma metabolome profile, (4) urine metabolome profile. The primary aim of the study is to evaluate correlation between the paired (challenge vs. rechallenge)liver enzyme responses. The expected result is that the subject s ALT response to rechallenge will be similar to his/her initial challenge response, thus yielding a high pair-wise correlation. The secondary aims of the study are to explore physiologic responses indicated by the transcriptomic and metabolomic data. Participants: Ten healthy subjects, five males and five females. Procedures: Subjects will be admitted to the GCRC for 11 days and on day 1, they will begin dosing with acetaminophen. Blood samples will be taken throughout the protocol to monitor for safety and for research analyses. Once discharged, subjects will wait 14 days and then be readmitted for identical study procedures as the first admission. There will be a followup visit at 14 days after discharge from the second admission and the study will then be completed.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：在本研究中，N=10 名在过去六个月内未接触过对乙酰氨基酚的合格正常健康志愿者（5 名男性，5 名女性）将被纳入 GCRC 并接受对乙酰氨基酚的挑战（APAP：1g Q6H，持续 10 天） 。然后，在家里避免 APAP 两周后，这些受试者将重新入院并重新接受挑战（1g Q6H，持续 10 天）。 每个 10 天挑战期间的关注结果是以下反应相对于基线观察到的最大变化：(1) 血清 log10ALT 和其他相关肝酶，(2) 外周血转录组指示的基因表达，(3) 血浆代谢组谱，（4）尿液代谢组谱。 该研究的主要目的是评估配对（挑战与再挑战）肝酶反应之间的相关性。预期结果是受试者对再次挑战的 ALT 反应将与他/她最初的挑战反应相似，从而产生高的成对结果 相关性。该研究的次要目的是探索转录组学和代谢组学数据表明的生理反应。 参与者：十名健康受试者，五名男性和五名女性。 程序：受试者将在 GCRC 住院 11 天，并在第 1 天开始服用对乙酰氨基酚。在整个方案中将采集血样以监测安全性和研究分析。出院后，受试者将等待 14 天，然后 重新入学的学习程序与第一次入学相同。第二次入院后 14 天将进行随访，然后完成研究。