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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：在本研究中，N=10名在过去6个月内未暴露于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激发（APAP：1g Q6 H，持续10天）。然后，在家中避免APAP两周后，这些受试者将重新入院并重新激发（1g Q6 H，持续10天）。 每次10天挑战期间关注的结局是以下应答相对于基线的最大观察变化：（1）血清log 10 ALT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。 本研究的主要目的是评价成对（激发与再激发）肝酶反应之间的相关性。预期结果是，受试者对再激发的ALT应答将与他/她的初始激发应答相似，因此产生高的成对应答。 相关性本研究的次要目的是探索转录组学和代谢组学数据所指示的生理反应。 对象：10名健康受试者，5男5女。 程序：受试者将入住GCRC 11天，并在第1天开始对乙酰氨基酚给药。将在整个方案期间采集血液样本，以监测安全性和进行研究分析。一旦出院，受试者将等待14天， 再次入院进行与首次入院相同的研究程序。将在第二次住院出院后14天进行随访访视，然后完成研究。