A Phase III Trial of Lorenzo's Oil in Adrenomyeloneuropathy

描述(由申请人提供)：研究人员建议完成一项关于三油酸甘油酯-三芥酸甘油酯(Lorenzo‘s Oil或LO)治疗成人X连锁肾上腺脑白质营养不良(X-ALD)的肾上腺脊髓神经病(AMN)的双掩蔽安慰剂对照研究。AMN是一种缓慢进展的远端轴索病变，累及脊髓的长束，不同于最常影响男孩和青少年的快速进展的炎症性脑形式。所有形式的X-ALD都与血浆和组织中超长链脂肪酸(VLCFA)的异常积聚有关。口服LO可在四周内使血浆VLCFA水平恢复正常。虽然之前对脑型X-ALD患者进行的LO治疗试验令人失望，但最近的研究表明，LO疗法在两种类型的X-ALD中是有益的：1)预防无症状男孩的神经损害；2)在AMN中，它似乎可以减缓进展速度。之前的研究都没有得到控制，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男性患者，以及120名X-ALD杂合子并患有AMN样综合症的女性患者。这项研究是在肯尼迪·克里格研究所和约翰·霍普金斯医疗机构的普通临床研究中心进行的。这项研究于2005年3月启动，由Westat公司协调。已有80名患者入选，入选工作将于2008年3月完成。LO组和安慰剂组的进展率将使用Kurtzke EDSS评分作为主要结果和各种次要结果进行比较。这项研究的一个新的部分是对新开发的标记物的使用和验证，即颈髓的磁化转移MRI和运动分析实验室中感觉强度和平衡的定量测试。这些标记物测试AMN最严重的神经系统部分的结构和功能。研究表明，与目前的技术相比，它们将允许对进展速度进行更敏感和快速的评估。这将加快对AMN治疗干预措施的评估。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.