Phase 2 Study of Deferiprone in the Treatment of NBIA

描述(由申请人提供)： 这是一项治疗一种罕见的遗传运动障碍患者的临床研究，这种疾病被称为神经退行性变伴脑铁蓄积(NBIA)。它的特点是神经系统的进行性退化和大脑中的铁积累，主要是基底节。NBIA主要影响儿童，目前还没有治愈方法。铁络合剂疗法已被提出，但由于缺乏有效穿越血脑屏障的铁络合剂，因此没有作为一种治疗方法进行系统研究。去铁酮是一种口服铁络合剂，国际上用于治疗全身铁超载，它可以跨越血脑屏障。临床报告表明，每天大约30毫克/公斤的去铁酮对有症状的脑铁过剩但没有全身铁蓄积的患者具有放射和临床疗效。这项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有效性。这项拟议的研究将是一项盲法、安慰剂对照的随机试验，在四年内对40名患者进行药物与安慰剂的2：1比率试验。符合条件的患者将是NBIA/PKAN突变阳性，年龄在8岁以上，他们在过去6个月中治疗失败，临床进展没有改善。一种使用大脑R2的MRI方案将测量大脑铁含量的变化。结果衡量标准将包括神经学和功能评估的改善。

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.