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

基本信息

批准号：
7500567
负责人：
ROBERT H SQUIRES
金额：
$ 20万
依托单位：
CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
依托单位国家：
美国
项目类别：
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/7500567
关键词：
Acetaminophen Acetylcysteine Active Sites Acute Acute Liver Failure Adolescent Adult Age Antidotes Autoimmune Hepatitis Biological Blood Coagulation Disorders Canada Cells Child Childhood Classification Clinical Clinical Data Clinical Trials Collaborations Collection DNA Data Data Set Defect Diagnosis Double-Blind Method Encephalopathies Enrollment Etiology Functional disorder Funding Funding Mechanisms Future Growth Immune Infant Ingestion Injury Intravenous Laboratories Link Liver Liver Failure Liver diseases Measures Modeling National Institute of Diabetes and Digestive and Kidney Diseases Natural Killer Cells Organ failure Outcome Pathogenesis Patients Pattern Placebos Population Prevalence Principal Investigator Proteins Purpose Recording of previous events Registries Reporting Research Ethics Committees Research Personnel Resources Role Safety Sampling Serum Site Specimen System Testing Tissues Toxic effect United States National Institutes of Health Viral hepatitis adduct age group cohort fatty acid metabolism fatty acid oxidation follow-up innovation liver transplantation male outcome forecast parent grant prospective randomized placebo controlled trial repository response

项目摘要

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, analyzetrends, 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, noveltreatment 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 examinethe safety and efficacy of IV NAC in children with ALF for whom there is no antidote or other specific treatment.

小儿急性肝衰竭研究小组（PALFSG）是第一个多中心的跨国合作确定，表征和制定针对婴儿，儿童和青少年的管理策略出现急性肝衰竭（ALF）。最初的资金和支持来自急性肝衰竭研究组（NIH 1R01-DK58369-01，威廉·李，医学博士，P.I）。该建议是建立独立的NIH 资金以支持该小儿财团的当前和未来活动。 PALFSG包括24个活动网站（美国21个，加拿大1个，英国2个），已收集了293的详细临床数据孩子们。我们已经重新定义了儿童的ALF，证明了儿童的ALF病因与成年人所见的不同之处在于，描述了自身免疫性肝炎相关的ALF的独特特征，现在正在使用静脉（IV）N-乙酰半胱氨酸（NAC）进行临床试验，以治疗非 - 对乙酰氨基酚Alf。本应用程序的具体目的是：（1）收集，维护，分析和报告 ALF儿童的临床，流行病学和结果数据，包括来自血清的信息，组织和DNA标本。未入学的其他NIH资助小儿的患者的长期结局数据财团将通过PALFSG收集。为了节省资源，NIDDK组织的存储库， DNA和血清将被利用。这些数据将用于开发预后的预测指标，分析剂，并向调查人员提供材料。（2）确定肝细胞损伤的未识别机制导致儿童的ALF。研究将评估脂肪酸氧化缺陷的影响NK细胞功能障碍和对乙酰氨基酚的ALF发病机理。通过这些研究，新颖可以制定策略。（3）继续并完成双盲，随机，安慰剂 NAC治疗非乙酰氨基酚ALF的对照试验。目的是检查安全性和功效没有解毒剂或其他特定治疗方法的ALF儿童的IV NAC。