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: 7485233
• 负责人: Gerald V. Raymond
• 金额: $ 34.99万
• 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 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485233
• 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）： 研究人员提议对 AMN（成人型 X 连锁肾上腺脑白质营养不良症 (X-ALD)）的 LO 疗法进行双盲、安慰剂对照研究。 AMN 进展缓慢。 它是一种累及脊髓长束的远端轴突病，与最常见影响男孩和青少年的快速进展的炎症性脑病不同。 AMN 分为两种形式。 “纯粹形式”的病理仅限于脊髓和周围神经，而 AMN 大脑表型则有炎症性脑受累的额外证据。 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 4 周内使 X-ALD 患者的血浆 VLCFA 水平恢复正常，并且在过去 14 年中进行了各种治疗试验。 虽然之前对脑部 X-ALD 患者进行 LO 的治疗试验令人失望，但最近的研究提供了大量证据表明它对两种类型的 X-ALD 有益：1) 提示性证据表明它可以使纯 AMN 的进展减慢 50%；2) 当对神经系统正常且脑部磁共振成像 (MRI) 正常的男孩使用时，可以起到预防作用。 之前的研究都是单一队列。 研究人员现在提出第一个安慰剂对照试验。 这将是一项为期三年的研究，涉及 120 名患有 AMN 的男性和 120 名女性。 该研究将由 Westat 协调。 将比较 LO 组和安慰剂组的进展率。 Kurtzke 扩展残疾状态量表 (EDSS) 评分将是主要结果衡量标准。 还将使用各种次要结果衡量标准。 现在人们认识到，50% 的杂合子会产生纯 AMN，这可能会导致严重的残疾。 这是第一项涉及 X-ALD 杂合子女性的治疗研究。