A Multi-Center Group to Study Acute Liver Failure in Children

研究儿童急性肝衰竭的多中心小组

• 批准号: 7122342
• 负责人: ROBERT H SQUIRES
• 金额: $ 64.62万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7122342
• 关键词: acetaminophen; acetylcysteine; adolescence (12-20); child (0-11); clinical research; clinical trials; cooperative study; disease /disorder etiology; drug adverse effect; epidemiology; fatty acid metabolism; human subject; human therapy evaluation; liver disorder chemotherapy; liver failure; natural killer cells; pathologic process; patient /disease registry; patient oriented research; prognosis; tissue resource /registry

DESCRIPTION (provided by applicant): The Pediatric Acute Liver Failure Study Group (PALFSG) is the first multi-center, multi-national collaboration to identify, characterize, and develop management strategies for infants, children and adolescents who present with acute liver failure (ALF). Initial funding and support came through the Acute Liver Failure Study Group (NIH 1R01-DK58369-01, William Lee, MD, P.I). This proposal is to establish independent NIH funding to support the current and future activities of this pediatric consortium. PALFSG includes 24 active sites (21 in the U.S., 1 in Canada and 2 in the U.K.) which have collected detailed clinical data from 293 children. We have already redefined ALF in children, demonstrated that the etiologies of ALF in children differs greatly from those seen in adults, described unique features of autoimmune hepatitis associated ALF, and are now conducting a clinical trial using intravenous (IV) N-acetylcysteine (NAC) to treat non- acetaminophen ALF. The Specific Aims of this application are: (1) To collect, maintain, analyze and report clinical, epidemiological, and outcome data in children with ALF, including information derived from serum, tissue, and DNA specimens. Long-term outcome data on patients not enrolled in other NIH-funded pediatric consortia will be collected through the PALFSG. To conserve resources, the NIDDK repositories for tissue, DNA and serum will be utilized. These data will be used to develop predictors of prognosis, analyze trends, and provide materials to investigators. (2) To identify unrecognized mechanisms of hepatocellular injury resulting in ALF in children. Studies will assess the impact of fatty acid oxidation defects, NK cell dysfunction, and acetaminophen on the pathogenesis of ALF. Through these studies, novel treatment strategies may be developed. (3) To continue and complete the double-blind, randomized, placebo controlled trial of NAC to treat non-acetaminophen ALF. The purpose is to examine the safety and efficacy of IV NAC in children with ALF for whom there is no antidote or other specific treatment

描述(由申请人提供)： 儿科急性肝功能衰竭研究小组(PALFSG)是第一个多中心、多国家合作，以确定、表征和制定婴儿、儿童和青少年急性肝功能衰竭(ALF)的管理策略。最初的资金和支持来自急性肝功能衰竭研究小组(NIH 1R01-DK58369-01，William Lee，MD，P.I.)。这项提议是为了建立独立的NIH基金，以支持这个儿科联盟目前和未来的活动。PALFSG包括24个活跃站点(21个在美国，1个在加拿大，2个在英国)他们收集了293名儿童的详细临床数据。我们已经重新定义了儿童的ALF，证明了儿童ALF的病因与成人的ALF有很大的不同，描述了自身免疫性肝炎相关性ALF的独特特征，目前正在进行一项临床试验，使用静脉注射(IV)N-乙酰半胱氨酸(NAC)治疗非对乙酰氨基酚ALF。此应用程序的具体目标是：(1)收集、维护、分析和报告ALF儿童的临床、流行病学和结局数据，包括来自血清、组织和DNA样本的信息。未加入NIH资助的其他儿科联盟的患者的长期结果数据将通过PALFSG收集。为了节约资源，将利用NIDDK组织、DNA和血清存储库。这些数据将被用来开发预测预后的指标，分析趋势，并为调查人员提供材料。(2)明确肝细胞损伤导致儿童ALF的未知机制。研究将评估脂肪酸氧化缺陷、NK细胞功能障碍和对乙酰氨基酚对ALF发病机制的影响。通过这些研究，可能会开发出新的治疗策略。(3)继续完成NAC治疗非对乙酰氨基酚ALF的双盲、随机、安慰剂对照试验。目的是检查静脉注射NAC在没有解药或其他特殊治疗的ALF儿童中的安全性和有效性。