Trial of Deferiprone in Parkinson's Disease
Trial of Deferiprone in Parkinson's Disease
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DOI：
10.1056/nejmoa2209254
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发表时间：
2022-12-01
影响因子：
158.5
通讯作者：
Moreau, Caroline
中科院分区：
文献类型：
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作者：
Devos, David;Labreuche, Julien;Moreau, Caroline
背景帕金森病患者的黑质中铁含量增加，并且可能有助于该疾病的病理生理学。早期研究表明，铁螯合剂去铁酮可以降低帕金森病患者的黑质纹状体铁含量，但其对疾病进展的影响尚不清楚。方法我们进行了一项多中心、2 期、随机、双盲试验，受试者为从未接受过左旋多巴治疗的新诊断帕金森病患者。参与者被分配（以 1:1 的比例）接受口服去铁酮治疗，剂量为每公斤体重 15 毫克，每天两次，或服用匹配的安慰剂，持续 36 周。除非认为控制症状有必要，否则停止多巴胺能治疗。主要结果是第 36 周时运动障碍协会赞助的统一帕金森病评定量表（MDS-UPDRS；范围为 0 至 260，分数越高表明损伤越严重）的总分变化。长达 40 周的次要和探索性临床结果包括运动和非运动残疾的测量。使用磁共振成像测量的脑铁含量也是一个探索性结果。 结果共有 372 名参与者入组； 186 人被分配接受去铁酮治疗，186 人被分配接受安慰剂治疗。去铁酮组中 22.0% 的参与者和安慰剂组中 2.7% 的参与者因症状进展而开始接受多巴胺能治疗。去铁酮组和安慰剂组的基线平均 MDS-UPDRS 总分分别为 34.3 分和 33.2 分，分别增加（恶化）15.6 分和 6.3 分（差异为 9.3 分；95% 置信区间为 6.3 至 12.2；P
BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P