INTRAVENOUS GAMMA GLOBULIN AS AN AGENT TO LOWER ALLOSENSITIZATION

静脉注射丙种球蛋白作为降低异敏性的药物

• 批准号: 6264952
• 负责人: Dawn Schmautz Milliner
• 金额: $ 2.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264952
• 关键词: chronic renal failure; clinical research; clinical trial phase I; gamma globulin; homologous transplantation; human subject; human therapy evaluation; immunotherapy; kidney transplantation; transplant rejection

Kidney tranplantation is the treatment of choice for most patients with end stage renal disease. However, immune sensitization to HLA antigens makes it difficult to find immunologically compatible renal allografts for up to 30 percent of the end stage renal disease population. Patients with a high percent of preformed for antibodies must wait considerably longer than the average two years for a suitably matched kidney, and in many cases are unable to be tranplanted at all. To date, there is no proven treatment that can result in the reduction in preformed antibodies. The hypotheses of the study are: Anti-idiotypic antibodies present in IVIG preparations have the ability to reduce anti-HLA antibody activity in vivo and in vitro; IVIG contains antibodies that block alloactivation in the standard MLR and could be beneficial in reducing allosensitization post transplant; IVIG inihibits anti-endothelial cell antibody activity and could have a beneficial effect in the prevention and treatment of vascular rejection episodes mediated by AECA; and IVIG treatment has the capacity to induce the blocking anti-idiotypic antibody synthesis by the recipients B cells and thus engender a long lasting suppression of alloreactive events and possibly enhance allograft survival. The proposed clinical trial is a multicenter study involving 100 patients from seven transplant centers scattered throughout the United States. Patients with end stage renal disease, awaiting renal tranplantation, and with preformed cytotoxic antibody levels of greater than 50 percent will be eligible for participation. Patients will be randomly assigned to receive either albumin placebo or IVIG at study entry and at 1, 2, 3, 12, and 24 months following enrollment. If the patient is transplanted any time during the 30 month trial, they will receive IVIG at the time of tranplantation and at 1, 2, 3, 12, and 24 months post transplantation.

肾移植是大多数终末期肾病患者的治疗选择。 然而，对HLA抗原的免疫致敏使得很难为高达30%的终末期肾病人群找到免疫相容的同种异体肾移植物。 具有高百分比的抗体的患者必须等待比平均两年长得多的时间才能获得合适的匹配肾脏，并且在许多情况下根本无法移植。 到目前为止，还没有经过证实的治疗方法可以减少预先形成的抗体。本研究的假设是：IVIG制剂中存在的抗独特型抗体具有降低体内和体外抗HLA抗体活性的能力; IVIG含有在标准MLR中阻断同种异体激活的抗体，并且可能有益于降低移植后的同种异体致敏性; IVIG抑制抗-内皮细胞抗体活性，并可能在预防和治疗由AECA介导的血管排斥反应事件中具有有益作用; IVIG治疗具有诱导受体B细胞阻断抗独特型抗体合成的能力，从而产生对同种异体反应事件的持久抑制，并可能提高同种异体移植物存活。拟议的临床试验是一项多中心研究，涉及来自美国7个移植中心的100名患者。终末期肾病患者，等待肾移植，并与预先形成的细胞毒性抗体水平大于50%将有资格参加。 患者将在入组研究时和入组后1、2、3、12和24个月随机分配接受白蛋白安慰剂或IVIG。 如果患者在30个月试验期间的任何时间接受移植，他们将在移植时和移植后1、2、3、12和24个月接受IVIG。