Phase 2 Study of Deferiprone in the Treatment of NBIA

去铁酮治疗 NBIA 的 2 期研究

• 批准号: 8709819
• 负责人: ELLIOTT P VICHINSKY
• 金额: $ 40万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8709819
• 关键词: Phase; Study; Deferiprone; Treatment; NBIA

DESCRIPTION (provided by applicant): This is a clinical study to treat patients with a rare genetic movement disorder known as neurodegeneration with brain iron accumulation (NBIA). It is characterized by the progressive degeneration of the nervous system and iron accumulation in the brain, primarily the basal ganglia. There is no cure for NBIA, which primarily affects children. Iron chelator therapy has been proposed, but not systematically studied as a treatment because of the lack of an iron chelator that effectively crosses the blood-brain barrier. Deferiprone, an oral iron chelator, used internationally for the treatment of systemic iron overload, crosses the blood-brain barrier. Clinical reports suggest deferiprone at approximately 30 mg/kg/day has radiographic and clinical efficacy in symptomatic patients with excess brain iron but no systemic iron accumulation. The primary aim of this study is to establish the safety of deferiprone in NBIA, and demonstrate efficacy of deferiprone in diminishing dystonic behaviors. The proposed research study will be a blinded, placebo-controlled, randomized trial of drug versus placebo in a 2:1 ratio in 40 patients over a four year period. Patients eligible will be NBIA/PKAN mutation positive, over 8 years of age, who have failed therapy and have shown clinical progression without improvement over the last six months. An MRI protocol using R2 of the brain will measure changes in brain iron content. Outcome measures will include improvement in neurologic and functional assessments.

描述（由申请人提供）： 这是一项治疗患有罕见遗传性运动障碍（称为脑铁累积神经变性（NBIA））患者的临床研究。其特征是神经系统进行性退化和大脑（主要是基底神经节）铁积聚。 NBIA 无法治愈，主要影响儿童。铁螯合剂疗法已经被提出，但由于缺乏有效穿过血脑屏障的铁螯合剂，因此没有系统地研究作为一种治疗方法。去铁酮是一种口服铁螯合剂，国际上用于治疗全身性铁超负荷，可穿过血脑屏障。临床报告表明，约 30 mg/kg/天的去铁酮对于脑铁过多但无全身铁蓄积的有症状患者具有放射学和临床疗效。本研究的主要目的是确定去铁酮在 NBIA 中的安全性，并证明去铁酮在减少肌张力障碍行为方面的功效。拟议的研究将是一项盲法、安慰剂对照、随机试验，以 2:1 的比例对 40 名患者进行药物与安慰剂的比较，为期四年。符合资格的患者为 NBIA/PKAN 突变阳性、年龄超过 8 岁、治疗失败且在过去六个月内表现出临床进展但无改善的患者。使用大脑 R2 的 MRI 协议将测量大脑铁含量的变化。结果测量将包括神经系统和功能评估的改善。