A Phase III Trial of Lorenzo's Oil in Adrenomyeloneuropathy

描述（由申请方提供）：研究者计划完成一项双盲安慰剂对照研究，研究三油酸甘油酯-三芥酸甘油酯（Lorenzo's Oil或LO）治疗肾上腺脊髓神经病（AMN），即成人型X连锁肾上腺脑白质营养不良（X-ALD）。AMN是一种缓慢进展的远端轴突病，涉及脊髓的长束，与最常见的影响男孩和青少年的快速进展的炎症性脑形式不同。所有形式的X-ALD都与血浆和组织中极长链脂肪酸（VLCFA）的异常积累有关。口服LO可在四周内使血浆VLCFA水平恢复正常。虽然以前在大脑型X-ALD患者中进行的LO治疗试验令人失望，但最近的研究表明，它在两种类型的X-ALD中是有益的：1）作为无症状男孩神经系统受累的预防剂; 2）在AMN中，它似乎减缓了进展速度。以前的研究都没有被控制，研究人员现在正在进行第一个安慰剂对照试验。 这项为期四年的研究将包括120名没有大脑受累证据的AMN男性，以及120名X-ALD杂合子并患有AMN样综合征的女性。该研究正在肯尼迪克里格研究所和约翰霍普金斯医疗机构的综合临床研究中心进行。该研究于2005年3月启动，由Westat Inc.协调。80名患者已入组，入组将于2008年3月完成。将使用Kurtzke EDSS评分作为主要结局和各种次要结局，比较LO组和安慰剂组的进展率。这项研究的一个新的部分是利用和验证新开发的标记物，即磁化转移MRI的颈脊髓和定量测试的感觉强度和平衡的运动分析实验室。这些标记物测试AMN中最严重参与的神经系统部分的结构和功能。这些研究表明，它们将允许比现有技术更敏感和快速地评估进展速度。这将加速AMN治疗干预的评估。这些技术也可能适用于其他脊髓疾病的研究。

DESCRIPTION (provided by applicant): The investigators propose to bring to completion a double-masked placebo controlled study of glyceryl trioleate-glyceryl trierucate (Lorenzo's Oil or LO) therapy in adrenomyeloneuropathy (AMN), the adult form of X-linked adrenoleukodystrophy (X-ALD). AMN is a slowly progressive distal axonopathy that involves the long tracts of the spinal cord and differs from the rapidly progressive inflammatory cerebral forms that most commonly affect boys and adolescents. All forms of X-ALD are associated with the abnormal accumulation of very long chain fatty acids (VLCFA) in plasma and tissues. The oral administration of LO normalizes plasma VLCFA levels within four weeks. While previous therapeutic trials of LO therapy in patients with the cerebral forms of X-ALD has been disappointing, recent studies suggest that it is beneficial in two types of X-ALD: 1) as a preventive of neurological involvement in asymptomatic boys; and 2) in AMN, where it appears to slow the rate of progression. None of the previous studies have been controlled, and the investigators are now conducting the first placebo-controlled trial. The four-year study will include 120 men with AMN who do not have evidence of cerebral involvement, and 120 women who are heterozygous for X-ALD and have an AMN-like syndrome. The study is being conducted at the Kennedy Krieger Institute and the General Clinical Research Center at the Johns Hopkins Medical Institutions. The study was initiated in March 2005 and is coordinated by Westat Inc. Eighty patients have been enrolled, and enrollment will be completed in March 2008. The rate of progression will be compared in the LO and placebo groups using the Kurtzke EDSS score as the primary outcome and a variety of secondary outcomes. A novel part of the study is the utilization and validation of newly developed markers, namely magnetization transfer MRI of the cervical spinal cord and quantitative tests of sensation strength and balance in the motion analysis laboratory. These markers test the structure and function of the parts of the nervous system that are most severely involved in AMN. The studies suggest that they will permit more sensitive and rapid assessment of the rate of progression than can be achieved with current techniques. This would accelerate the evaluation of therapeutic interventions in AMN. These techniques may also be applicable to the study of other spinal cord disorders.