Focal Segmental Glomerulosclerosis in Young Patients

年轻患者的局灶节段性肾小球硬化

• 批准号: 6665340
• 负责人: SANDRA L. WATKINS
• 金额: $ 62.93万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665340
• 关键词: ACE inhibitors; FK506; adolescence (12-20); clinical research; clinical trials; combination chemotherapy; corticosteroids; cyclophosphamide; drug adverse effect; glomerular filtration rate; glomerulosclerosis; human subject; human therapy evaluation; kidney disorder chemotherapy; kidney function; oral administration; outcomes research; pathologic process; pediatric pharmacology; proteinuria; remission /regression; renal failure; steroids; young adult human (21-34)

DESCRIPTION (provided by applicant): Primary focal segmental glomerulosclerosis (FSGS) is an organ-specific autoimmune disease with poor response to immunomodulating agents and a poor prognosis. The relatively small number of children and young adults with FSGS and the lack of compelling prospective double-blind randomized multi-center therapeutic studies have hampered the formulation of an evidenced-based therapeutic approach. Cyclophosphamide and calcineurin inhibitors act on different sites of the cytotoxic T cell cycle and support the hypothesis of synergistic effectiveness of combination therapy. We propose a double-blind, randomized, controlled trial comparing A) sequential cyclophosphamide followed by tacrolimus with oral steroids and angiotensin-converting enzyme inhibitors (ACEI) with B) tacrolimus with oral steroids and ACEI. We will develop a database to compare the response to each treatment arm with respect to the primary end-point: reduction in proteinuria. The secondary outcomes will be remission rate, relapse frequency, progression of renal failure as measured by glomerular filtration rate, total cumulative corticosteroid dose and adverse events. Patient age, ethnicity, gender, renal histological classification, podocin mutation status, baseline proteinuria and baseline renal excretory function will be correlated with primary and secondary outcomes. We have formed a Western Pediatric Nephrology Clinical Trials Group consisting of 28 pediatric centers with collaborating adult nephrologists. These centers have a rich history of successful collaborative studies in the past. From our initial survey of patients in the past two years, we have a more than sufficient patient population-base from which to recruit to ensure enrollment of at least 100 study subjects in our region. We will participate as a regional center in the collaborative, multicenter randomized controlled clinical trial of therapy to improve the clinical course of children and young adults with primary FSGS as stated in the RFA.

描述（由申请人提供）： 原发性局灶节段性肾小球硬化症（FSGS）是一种器官特异性自身免疫性疾病，对免疫调节剂反应较差，预后较差。患有 FSGS 的儿童和年轻人数量相对较少，并且缺乏令人信服的前瞻性双盲随机多中心治疗研究，阻碍了循证治疗方法的制定。环磷酰胺和钙调神经磷酸酶抑制剂作用于细胞毒性 T 细胞周期的不同位点，支持联合治疗具有协同效应的假设。我们提出了一项双盲、随机、对照试验，比较 A) 序贯环磷酰胺随后使用他克莫司联合口服类固醇和血管紧张素转换酶抑制剂 (ACEI) 与 B) 他克莫司联合口服类固醇和 ACEI。我们将开发一个数据库来比较每个治疗组对主要终点（蛋白尿减少）的反应。次要结局是缓解率、复发频率、通过肾小球滤过率衡量的肾衰竭进展、总累积皮质类固醇剂量和不良事件。患者年龄、种族、性别、肾脏组织学分类、podocin 突变状态、基线蛋白尿和基线肾排泄功能将与主要和次要结果相关。我们成立了一个西方儿科肾脏病临床试验小组，由 28 个儿科中心和成年肾脏病专家合作组成。这些中心过去有着丰富的成功合作研究历史。从我们过去两年对患者的初步调查来看，我们有足够的患者群体基础来招募，以确保在我们地区招募至少 100 名研究对象。我们将作为区域中心参与协作、多中心随机对照治疗临床试验，以改善 RFA 中所述的原发性 FSGS 儿童和年轻人的临床病程。