A Phase III Trial of Lorenzo's Oil in Adrenomyeloneuropathy

洛伦佐油治疗肾上腺脊髓神经病的 III 期试验

• 批准号: 7652513
• 负责人: Gerald V. Raymond
• 金额: $ 64.43万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-18 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7652513
• 关键词: 3-Dimensional; Admission activity; Adolescent; Adrenoleukodystrophy; Adrenomyeloneuropathy; Adult; Affect; Biochemical; Brain; Cerebrum; Cervical spinal cord structure; Childhood; Clinical; Clinical Assessment Tool; Clinical Research; Communities; Demyelinations; Disabled Persons; Disease Progression; Distal; Endocrine; Enrollment; Equilibrium; Esthesia; Evaluation; Exhibits; Imagery; Imaging Techniques; Inflammatory; Institutes; Institution; Intervention; Laboratories; Lorenzo' s oil; Magnetic Resonance Imaging; Male Adolescents; Masks; Measurement; Measures; Medical; Modification; Motion; Multiple Sclerosis; Mutation Analysis; Nervous System Part; Nervous system structure; Neurologic; Nutritional status; Oral Administration; Pathogenesis; Pathology; Patients; Phase III Clinical Trials; Phenotype; Placebo Control; Placebos; Plasma; Preventive; Process; Research Personnel; Sensorimotor functions; Severities; Speed; Spinal Cord Diseases; Spinal Cord Part; Spinal Cord Tract; Structure; Surrogate Markers; Syndrome; Techniques; Testing; Therapeutic Intervention; Therapy Clinical Trials; Tissues; Upper arm; Validation; Very Long Chain Fatty Acid; Woman; axonopathy; boys; cohort; design; disability; dorsal column; handicapping condition; innovation; insight; kinematics; men; muscle strength; neuroimaging; novel; placebo controlled study; primary outcome; programs; reconstruction; secondary outcome; standard measure; tool; trierucate; vibration

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.

描述（由申请人提供）：调查人员建议在肾上腺瘤肾上腺疾病（lorenzo's Oil或lo）中完成双层掩盖的安慰剂对照研究（lorenzo's Oil或lo）疗法（AMN），成人形式的X系列形式的X系列型脂肪肌发育植物（X- X- X- X- X- X- X- X- X- X-）。 AMN是一种缓慢进行的远端轴突病，涉及脊髓的长段，与快速进行性炎症性脑形式不同，最常见地影响男孩和青少年。所有形式的X-ald都与血浆和组织中非常长的链脂肪酸（VLCFA）的异常积累有关。 LO的口服给药使血浆VLCFA水平在四个星期内归一化。虽然先前在X-ALD脑形式的患者中对LO治疗的治疗试验令人失望，但最近的研究表明，在两种类型的X-ALD中，它是有益的：1）作为预防无症状男孩神经系统参与的预防。 2）在AMN中，它似乎会减慢进展速度。先前的研究都没有受到控制，研究人员现在正在进行第一次安慰剂对照试验。 这项为期四年的研究将包括120名没有脑部参与证据的AMN男性，还有120名X-Ald杂合子并患有AMN样综合征的女性。这项研究正在肯尼迪·克里格研究所（Kennedy Krieger Institute）和约翰·霍普金斯医疗机构的一般临床研究中心进行。该研究于2005年3月开始，由Westat Inc.进行了协调。已招募了80名患者，并将在2008年3月完成入学率。将使用Kurtzke EDSS评分作为主要结果和各种次要灭绝效果的LO和安慰剂组比较LO和安慰剂组的进展。该研究的一个新部分是对新开发的标记物的利用和验证，即颈脊髓的磁化转移MRI以及运动分析实验室中感觉强度和平衡的定量测试。这些标记测试了最严重参与AMN的神经系统部分的结构和功能。研究表明，与当前技术相比，它们将允许对进展速率进行更敏感和快速评估。这将加速对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。

项目成果

Genetic variants of methionine metabolism and X-ALD phenotype generation: results of a new study sample.

蛋氨酸代谢和 X-ALD 表型生成的遗传变异：新研究样本的结果。

• DOI: 10.1007/s00415-009-5114-6
• 发表时间: 2009
• 期刊: Journal of neurology
• 影响因子: 6
• 作者: Semmler,Alexander;Bao,Xinhua;Cao,Guangna;Köhler,Wolfgang;Weller,Michael;Aubourg,Patrick;Linnebank,Michael
• 通讯作者: Linnebank,Michael