THERAPEUTIC TRIALS OF X-LINKED ALD: PHASE III; LORENZO*

X 连锁 ALD 的治疗试验：第三阶段；

• 批准号: 7061895
• 负责人: HUGO W MOSER
• 金额: $ 34.81万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7061895
• 关键词: THERAPEUTIC; TRIALS; LINKED; ALD; PHASE

DESCRIPTION (provided by applicant): The investigators propose to conduct a double-masked, placebo-controlled study of LO therapy in AMN, the adult form of X-Iinked adrenoleukodystrophy (X-ALD). AMN is slowly progressive. It is a 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. AMN is subdivided into two forms. The "pure form" in which pathology is confined to spinal cord and peripheral nerve, and the AMN cerebral phenotype in which there is additional evidence of inflammatory cerebral involvement. 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 in X-ALD patients within four weeks, and various therapeutic trials have been conducted during the last 14 years. While previous therapeutic trials of LO in patients with the cerebraI forms of X-ALD were disappointing, recent studies provide considerable evidence that it is beneficial in two types of X-ALD: 1) suggestive evidence that it slows progression of pure AMN by 50% and 2) preventive effect when administered to boys who are neurologically normal and have normal brain magnetic resonance imaging (MRI). Previous studies have been single cohort. The investigators now propose the first placebo-controlled trial. It will be a three-year study that will involve 120 men and 120 women with AMN. The study will be coordinated by Westat. The rate of progression will be compared in the LO and placebo groups. The Kurtzke Expanded Disability Status Scale (EDSS) score will be the primary outcome measure. A variety of secondary outcome measures will also be used. It is now recognized that 50% of heterozygous develop pure AMN which may lead to considerable disability. This is the first therapeutic study that also involves women heterozygous for X-ALD.

描述(由申请人提供)： 研究人员建议对成人型X连锁肾上腺脑白质营养不良(X-ALD)的AMN进行双掩蔽、安慰剂对照的LO治疗研究。AMN是缓慢进步的。这是一种累及脊髓长束的远端轴索病变，不同于最常影响男孩和青少年的快速进行性炎症性脑形式。AMN细分为两种形式。病理仅限于脊髓和周围神经的“纯形式”，以及AMN的脑表型，其中有炎症性脑损害的额外证据。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可以在四周内使X-ALD患者的血浆VLCFA水平恢复正常，在过去的14年里，已经进行了各种治疗试验。虽然之前对大脑I型X-ALD患者进行的LO治疗试验令人失望，但最近的研究提供了相当多的证据表明，它在两种类型的X-ALD中是有益的：1)提示证据表明，它可以将单纯AMN的进展减慢50%；2)当对神经学正常和脑磁共振成像(MRI)正常的男孩使用LO时，具有预防作用。 之前的研究都是单队列研究。研究人员现在提出了第一个安慰剂对照试验。这将是一项为期三年的研究，将有120名男性和120名女性患有AMN。这项研究将由Westat协调。LO组和安慰剂组的进展速度将进行比较。Kurtzke扩展残疾状态量表(EDSS)评分将是主要的结果衡量标准。还将使用各种次要结果衡量标准。现在人们认识到，50%的杂合子会发展成纯净的AMN，这可能会导致相当大的残疾。这是第一个也涉及X-ALD杂合子女性的治疗性研究。