Pediatric Acute Liver Failure (PALF) TReatment for ImmUne Mediated PathopHysiology (TRIUMPH)

小儿急性肝衰竭 (PALF) 免疫介导病理生理学治疗 (TRIUMPH)

• 批准号: 9678070
• 负责人: Estella M. Alonso
• 金额: $ 38.42万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9678070
• 关键词: Acetaminophen; Acute; Acute Liver Failure; Adrenal Cortex Hormones; Adverse effects; Affect; Anti-inflammatory; Antigen Receptors; Antithymoglobulin; Aplastic Anemia; Biological Markers; Blood; Blood Circulation; Blood specimen; CD8-Positive T-Lymphocytes; Caring; Case Study; Cause of Death; Cells; Child; Childhood; Chronic Childhood Arthritis; Clinical; Cytokine Receptors; Data; Data Quality; Diagnosis; Disease; Disease Progression; Dose; Double-Blind Method; Effectiveness; Enrollment; Ensure; Environmental Exposure; Equilibrium; Equus caballus; Etiology; Evaluation; Event; Failure; Foundations; Functional disorder; Future; Goals; Grant; Health; Hepatic; Hepatocyte; Immune; Immune response; Immunophenotyping; Infection; Infiltration; Inflammation; Inflammatory; Inflammatory Infiltrate; Inflammatory Response; Institutional Review Boards; Intravenous; Knowledge; Life; Liver; Liver diseases; Manuals; Measures; Mediating; Methylprednisolone; National Institute of Diabetes and Digestive and Kidney Diseases; Natural regeneration; Network Infrastructure; North America; Online Systems; Organ failure; Outcome; Participant; Pathogenesis; Patient Outcomes Assessments; Patients; Pattern; Pharmaceutical Preparations; Phase; Phenotype; Physicians; Placebos; Population; Population Analysis; Process; Prognostic Marker; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Rare Diseases; Rehabilitation therapy; Research; Research Personnel; Resolution; Resources; Risk; Role; Safety; Sampling; Severities; Signal Transduction; Site; Steroids; Survival Rate; System; T cell response; T-Cell Activation; T-Lymphocyte; Testing; Therapeutic immunosuppression; Time; Tissues; Toxic effect; Treatment Failure; Treatment outcome; Virus; Work; adaptive immune response; arm; biobank; effective therapy; efficacy testing; experience; follow-up; functional status; healing; immune activation; immune function; immunoregulation; improved; liver biopsy; liver injury; liver transplantation; mortality; operation; outcome forecast; peripheral blood; prevent; primary outcome; programs; randomized placebo controlled trial; rare condition; recruit; repository; research study; response; secondary outcome; theories; tool; treatment center; treatment trial

PROJECT SUMMARY Pediatric Acute Liver Failure (PALF) is a rare, devastating condition that affects an estimated 250 children per year in North America, causing death in approximately 15% and the need for liver transplantation (LT) in an additional 20-30%. In the majority of cases, a specific cause of the liver injury is never determined. Recent research conducted in these patients supports the theory that many of these patients have liver injury related to an abnormal immune response to everyday infections or environmental exposures. Studies have recently implicated T lymphocytes as the central drivers of the inflammatory process. Physicians caring for PALF patients are searching for therapies that quiet this T cell response, dampen the inflammatory cascade and allow the patient’s remaining liver cells to heal and regenerate. Clinical experience in children with abnormal immune responses associated with other disease states such as Systemic Juvenile Idiopathic Arthritis and Acquired Aplastic Anemia has demonstrated that both high dose corticosteroids and equine anti- thymocyte globulin can suppress immune responses and reverse progressive tissue damage. The goal of the proposed research network is to support a treatment trial of immunosuppressive therapy using high dose corticosteroids or equine anti-thymocyte globulin to reverse harmful inflammatory immune responses in children with PALF to prevent further disease progression and reduce mortality and LT in this population. We propose a double-blind, three arm, randomized, placebo controlled trial of high dose methylprednisolone or equine anti-thymocyte globulin. We will test the hypothesis that survival with native liver will be significantly higher in patients receiving immunosuppressive therapy as compared to patients that receive placebo. We will also determine the safety of immunosuppressive therapy in PALF patients and define the balance between risk of side-effects and treatment benefit. Our outcomes will include not only clinical end-points such as patient survival, time to resolution of disease and adverse health events, but also measures of patient reported outcomes during rehabilitation from the illness. Trial participants will provide blood and liver samples that will be examined to better understand their immune responses, especially that of T lymphocytes, in both the circulation and in the liver. Samples will be stored in a repository to support future studies exploring new aspects of this rare disease.

项目总结