Phase 1-2 trial of Gamunex (intravenous gammaglobulin) for Sickle Cell Acute Pain

Gamunex（静脉注射丙种球蛋白）治疗镰状细胞性急性疼痛的 1-2 期试验

• 批准号: 8447708
• 负责人: DEEPA G MANWANI
• 金额: $ 20万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-20 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447708
• 关键词: Phase; trial; Gamunex; intravenous; gammaglobulin

Sickle cell disease is the most common hemoglobinopathy in the world, and, in the United States, affects approximately 1 in 360 African Americans and 1 in 1200 Latinos. Small vessel occlusion, or vaso-occlusion, is the primary pathology leading to clinical complications of this disease. The most frequent manifestation of vaso-occlusion is the acute pain episode (crisis), which often requires hospitalization and narcotic use, thus exacting an economic, social, and psychological toll on afflicted individuals. Standard of care is inadequate, there being no specific therapies that target ongoing acute pain episodes. Mouse models have shown that leukocytes adherent to blood vessel endothelium play a crucial role in vaso-occlusion, probably through their subsequent interaction with sickle red blood cells. Further work has shown that intravenous gammaglobulin (IVIG) administered either prior to or after the induction of vaso-occlusion rapidly and dramatically reduces leukocyte adhesion to endothelium and subsequent red cell interactions, leading to a marked increase in survival. Based on this work , we propose to conduct a randomized, double-blind, placebo- controlled, dose-escalation Phase I-II trial to study the safety and efficacy of a single dose of IVIG compared to normal saline placebo administered to patients with sickle cell anemia admitted to the hospital with an uncomplicated acute pain episode. A total of 52 subjects will be enrolled. We hypothesize that IVIG will act quickly to reduce vaso-occlusion and thus pain scores, narcotic use, and length of hospitalization. We will also investigate the physiological effects of IVIG in patients with sickle cell disease by measuring the adhesion receptors involved in leukocyte adherence to endothelium and red blood cell-leukocyte interactions, microcirculatory blood flow, and serum markers of hemolysis. Completion of this trial will allow us to submit by the end of the grant period an NIH application to expand this trial into a Phase III trial or to test, in Phase I-II trials, newly identified agents that interfere with the molecular mechanism of vaso-occlusion.

镰状细胞病是世界上最常见的血红蛋白病，在美国 州，影响了大约三十六分之一的非洲裔美国人和一千二百分之一的拉丁裔美国人。小船 闭塞或血管闭塞是导致这种疾病临床并发症的主要病理学 疾病。血管闭塞最常见的表现是急性疼痛发作（危机）， 这往往需要住院治疗和使用麻醉品，从而对经济、社会和 对受影响者造成的心理伤害。护理标准不充分，没有具体规定 针对持续急性疼痛发作的疗法。 小鼠模型表明，粘附在血管内皮上的白细胞发挥着 在血管闭塞中发挥关键作用，可能是通过它们随后与镰状红血的相互作用 细胞。进一步的研究表明，静脉注射丙种球蛋白 (IVIG) 在之前或之后施用 诱导血管闭塞后，迅速并显着降低白细胞粘附 内皮细胞和随后的红细胞相互作用，导致存活率显着增加。 基于这项工作，我们建议进行一项随机、双盲、安慰剂试验 受控、剂量递增 I-II 期试验，研究单剂量 IVIG 的安全性和有效性 与对入院的镰状细胞性贫血患者施用的生理盐水安慰剂进行比较 因无并发症的急性疼痛发作而入院。总共将招收52个科目。我们 假设 IVIG 将迅速发挥作用，减少血管闭塞，从而减少疼痛评分、麻醉剂的使用、 以及住院时间。我们还将研究 IVIG 对患者的生理影响 通过测量参与白细胞粘附的粘附受体来诊断镰状细胞病 内皮和红细胞-白细胞相互作用、微循环血流量和血清 溶血标志物。 完成这项试验将使我们能够在资助期结束前提交 NIH 申请将该试验扩展为 III 期试验，或在 I-II 期试验中测试新发现的 干扰血管闭塞分子机制的药物。