Biliary Atresia Clinical Research Consortium

胆道闭锁临床研究联盟

• 批准号: 7244284
• 负责人: SAUL J. KARPEN
• 金额: $ 33.29万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-07 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7244284
• 关键词: Address; Area; Autologous; B-Lymphocytes; Biliary Atresia; Cell Line; Cessation of life; Child; Child Care; Childhood; Clinical Research; Cytotoxic T-Lymphocytes; Data; Databases; Defect; Diagnosis; Diagnostic Procedure; Disease; EBV-Specific Cytotoxic T-Lymphocyte; Enrollment; Equilibrium; Etiology; Genes; Human Herpesvirus 4; Human Resources; Immunosuppression; Individual; Infusion procedures; Institution; Life; Liver; Liver diseases; Lymphoproliferative Disorders; Medical; Morbidity - disease rate; Mutation; Nature; Operative Surgical Procedures; Outcome; Patient Care; Patients; Pediatric Hospitals; Protocols documentation; Research Ethics Committees; Resources; Services; Staging; Surgical Management; T-Lymphocyte; Texas; Therapeutic immunosuppression; Transplant Recipients; Transplantation; United States; United States Food and Drug Administration; With laterality; base; immunoregulation; improved; liver transplantation; novel

DESCRIPTION (provided by applicant): Biliary atresia (BA) is a disease of unknown etiology that, if undiagnosed leads almost universally to death. Even with diagnosis and appropriate treatment, there is tremendous morbidity associated with BA. There are 250-400 patients diagnosed annually with this disorder in the United States. Approximately 60-80% of these patients will develop end-stage liver disease, and will require liver transplantation. Currently, BA is the main indication for liver transplantation in children in the United States. The lack of a nationwide network to study and treat these patients significantly impairs clinical and research advancements, since each individual center sees relatively few BA patients. As a consequence, there are few data about basic issues, which could fundamentally change the outcome for these patients, e.g., etiology, diagnostic techniques, medical and surgical management, and post-transplantation therapy. The formation of a nationwide Biliary Atresia Clinical Research Consortium (BACRC) will allow such data to be collected, leading to improved outcomes for BA patients nationwide. At the Texas Children's Hospital (TCH), the largest pediatric hospital in the United States, we propose to use the resources of the institution and the dedicated Texas Children's Liver Center to enroll and care for patients in the BACRC. The Texas Children's Liver Center provides a full-service and coordinated approach to the care of children with liver disease, by synthesizing the involvement of medical, surgical, and transplant personnel. There are 3 areas of need of BA patients that the Texas Children's Liver Center proposes to address in this application: 1.) develop a database to gather relevant patient data and enhance participation in the BACRC;2.) explore an underlying etiology of BA by determining if BA patients with laterality defects have mutations in the lnversin (Invs) gene; and 3.) explore a novel treatment involving infusion of patient-derived cytotoxic T lymphocyte (CTL) cell lines directed against Epstein Barr Virus (EBV) for the most devastating of post-transplant outcomes that preferentially occurs in pediatric transplant recipients: Post-Transplant Lymphoproliferative Disorder (PTLD). Autologous infusion of EBV-specific CTL lines may restore the natural balance of immunomodulation of EBV-transformed B cells that is suppressed by the inherent nature of current T-cell based immunosuppression. An IRB, FDA, and NIH-approved protocol for this therapy is currently in place at the TCH and involves the support of the General Clinical Research Center. It is only by engaging in a nationwide multi-institutional approach that we can begin to discover information to understand and treat patients with life-long needs like BA.

描述（由申请人提供）： 胆道闭锁（BA）是一种病因不明的疾病，如果未确诊，几乎普遍导致死亡。即使有诊断和适当的治疗，有巨大的发病率与BA。在美国，每年有250-400名患者被诊断患有这种疾病。这些患者中约有60-80%将发展为终末期肝病，并需要肝移植。目前，BA是美国儿童肝移植的主要适应症。缺乏一个全国性的网络来研究和治疗这些患者，这严重损害了临床和研究的进展，因为每个中心看到的BA患者相对较少。因此，关于基本问题的数据很少，这些基本问题可能从根本上改变这些患者的结果，例如，病因学、诊断技术、内科和外科治疗以及移植后治疗。全国性胆道闭锁临床研究联盟（BACRC）的成立将允许收集此类数据，从而改善全国BA患者的结局。在美国最大的儿科医院德克萨斯儿童医院（TCH），我们建议利用该机构的资源和专门的德克萨斯儿童肝脏中心来招募和护理BACRC中的患者。德克萨斯州儿童肝脏中心通过综合医疗，手术和移植人员的参与，为肝病儿童的护理提供全面服务和协调的方法。德克萨斯州儿童肝脏中心建议在本申请中解决BA患者的3个需求领域：1.建立数据库，以收集相关的病人数据，并加强参与BACRC;2.）通过确定具有偏侧性缺陷的BA患者是否具有反转蛋白（Invs）基因中的突变来探索BA的潜在病因;以及3.）探索一种新的治疗方法，包括输注患者源性细胞毒性T淋巴细胞（CTL）细胞系，针对Epstein巴尔病毒（EBV），用于治疗最具破坏性的移植后结局，这些结局优先发生在儿科移植受者中：移植后恶性增殖性疾病（PTLD）。EBV特异性CTL系的自体输注可以恢复EBV转化的B细胞的免疫调节的自然平衡，该平衡被当前基于T细胞的免疫抑制的固有性质所抑制。一个IRB，FDA和NIH批准的治疗方案目前在TCH实施，并得到了一般临床研究中心的支持。 只有通过在全国范围内采取多机构的方法，我们才能开始发现信息，以了解和治疗像BA这样有终身需求的患者。