COOPERATIVE CLINICAL TRIALS IN RENAL TRANSPLANTATION

肾移植的合作临床试验

• 批准号: 2066448
• 负责人: J THOMAS ROSENTHAL
• 金额: $ 7.31万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2066448
• 关键词: FK506; acute renal failure; adult human (21+); blood chemistry; child (0-11); clinical trials; cooperative study; cyclosporines; dosage; drug adverse effect; drug screening /evaluation; fine needle aspiration; human subject; human therapy evaluation; hypertension; immunosuppression; immunosuppressive; insulin dependent diabetes mellitus; kidney function; kidney transplantation; macrolide antibiotics; magnetic resonance imaging; neoplasm /cancer; opportunistic infections; pharmacokinetics; postmortem; renal toxin; steroids; transplantation immunology; urinalysis

The purpose of this project is to test the efficacy and safety of the new immune suppressive agent FK506 as baseline immune suppression in adult and pediatric cadaver renal transplants to attempt to improve the results in kidney transplantation over results currently obtained with conventional Cyclosporine based immune suppression. This will be accomplished by a randomized, open labeled, controlled clinical trial comparing standard Cyclosporine with FK506 based immune suppression. Both groups will receive steroid with an identical regimen. Rejection will be treated in a similar fashion in both groups with bolus steroids and OKT3. Primary outcome variables will be graft and patient survival one and two years after transplantation. Patients will be followed out to five years to determine long term safety. Detection and diagnosis of rejection will be facilitated by fine needle aspiration, core biopsy, and measurement of peripheral and intragraft cytokines. Studies will be carried out to attempt to refine the diagnostic accuracy of fine needle aspiration by use of DNA applification of individual lymphocytes to detect intragraft immune activation. Pharmacokinetic studies of FK506 will enable precise therapeutic dose ranges to be developed. Important secondary outcome variables will be compared. These include drug nephrotoxicity, hypertension, incidence of opportunistic infections, hyperlipidemia, diabetogenesis, growth in children, and compliance. Standard measurements of renal function will be augmented by NMR examination of kidneys prior to implantation, fine needle aspiration to quantitate degrees of tubular damage, and isotope scans to more precisely quantitate kidney function. After one year post transplant a steroid withdrawal protocol will be instituted in a group of patients with stable renal function to determine if FK506 is potentially more steroid sparing than Cyclosporine. Patients will be closely monitored for evidence of acute rejection prior to institution. In vitro measurements of immune functioning will be carried out simultaneously to attempt to predict which patients can prospectively be safely steroid withdrawn. If the results of the randomized trial show a superiority of FK506, then further refinements of its use will be developed, or it will be tested against newer drugs. Depending on the degree of improvement living related recipients will be included in such trials in the fourth and fifth years. If there is not a significant improvement with FK506, then newer drugs which are currently in animal development in our laboratories will be tested against Cyclosporine.

该项目的目的是测试新的功能和安全性 免疫抑制剂FK506作为成人的基线免疫抑制 小儿尸体肾移植，试图改善结果 肾脏移植超过当前使用常规结果获得的结果 基于环孢菌素的免疫抑制。 这将通过 比较标准的随机，打开标签，对照临床试验 基于FK506的免疫抑制的环孢菌素。 两组将收到 类固醇具有相同的方案。 拒绝将以类似的对待 两组均具有类固醇和OKT3的时尚。 主要结局变量将是移植物，患者生存1和两个 移植后几年。 患者将遵循五年 确定长期安全。 检测和诊断被排斥将 通过细针抽吸，核心活检和测量 外周和内部细胞因子。 研究将进行 尝试通过使用来完善细针吸入的诊断准确性 单个淋巴细胞的DNA应用以检测​​内部免疫 激活。 FK506的药代动力学研究将使精确 要开发的治疗剂量范围。 将比较重要的次要结果变量。 这些包括药物 肾毒性，高血压，机会性感染的发病率， 高脂血症，糖尿病生成，儿童的生长和依从性。 NMR将增强肾功能的标准测量 检查肾脏在植入之前，精细的针头抽吸 定量管状损伤程度，同位素扫描到更精确 定量肾功能。 移植后一年后，类固醇提取方案将是 在一组稳定肾功能的患者中成立以确定 如果FK506可能比环孢霉素更具类固醇的保留。 患者 将密切监视以获取急性排斥之前的证据 机构。 将进行免疫功能的体外测量 同时尝试预测哪些患者可以前瞻性 安全地拔出类固醇。 如果随机试验的结果显示出FK506的优势，则 将开发其使用的进一步改进，否则将进行测试 反对新的药物。 取决于改善生活的程度 在第四和第五年，接收者将包括在此类试验中。 如果FK506没有显着改善，那么较新的药物 目前正在我们实验室中的动物发展中将 针对环孢菌素测试。