Saute Jonas Alex Morales, de Castilhos Raphael Machado, Monte Thais Lampert, Schumacher-Schuh Artur Francisco, Donis Karina Carvalho, D'Ávila Rui, Souza Gabriele Nunes, Russo Aline Dutra, Furtado Gabriel Vasata, Gheno Tailise Conte, de Souza Diogo Onofre Gomes, Portela Luis Valmor Cruz, Saraiva-Pereira Maria-Luiza, Camey Suzi Alvez, Torman Vanessa Bielefeld Leotti, de Mello Rieder Carlos Roberto, Jardim Laura Bannach
Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Medical Genetics, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
Mov Disord. 2014 Apr;29(4):568-73. doi: 10.1002/mds.25803. Epub 2014 Jan 7.
Because lithium exerts neuroprotective effects in preclinical models of polyglutamine disorders, our objective was to assess the safety and efficacy of lithium carbonate (0.5-0.8 milliequivalents per liter) in patients with Machado-Joseph disease (spinocerebellar ataxia type 3 [MJD/SCA3]).
For this phase 2, single-center, double-blind, parallel, placebo-controlled trial (ClinicalTrials.gov identifier NCT01096082), 62 patients who had MJD/SCA3 with a disease duration ≤10 years and an independent gait were randomly assigned (1:1) to receive either lithium or placebo.
After 24 weeks, 169 adverse events were reported, including 50.3% in the lithium group (P = 1.00; primary safety outcome). Sixty patients (31 in the placebo group and 29 in the lithium group) were analyzed for efficacy (intention-to-treat analysis). Mean progression between groups did not differ according to scores on the Neurological Examination Score for the Assessment of Spinocerebellar Ataxia (NESSCA) after 48 weeks (-0.35; 95% confidence interval, -1.7 to 1.0; primary efficacy outcome). The lithium group exhibited minor progression on the PATA speech-rate (P = 0.002), the nondominant Click Test (P = 0.023), the Spinocerebellar Ataxia Functional Index (P = 0.003), and the Composite Cerebellar Functional Score (P = 0.029).
Lithium was safe and well tolerated, but it had no effect on progression when measured using the NESSCA in patients with MJD/SCA3. This slowdown in secondary outcomes deserves further clarification.
由于锂在多聚谷氨酰胺疾病的临床前模型中具有神经保护作用，我们的目的是评估碳酸锂（每升0.5 - 0.8毫当量）对马查多 - 约瑟夫病（脊髓小脑共济失调3型 [MJD/SCA3]）患者的安全性和有效性。
在这项2期、单中心、双盲、平行、安慰剂对照试验（ClinicalTrials.gov标识符NCT01096082）中，62例疾病持续时间≤10年且具有独立步态的MJD/SCA3患者被随机分配（1:1）接受锂或安慰剂治疗。
24周后，共报告了169例不良事件，其中锂组占50.3%（P = 1.00；主要安全性结局）。对60例患者（安慰剂组31例，锂组29例）进行了疗效分析（意向性分析）。48周后，根据脊髓小脑共济失调评估神经学检查评分（NESSCA），两组间的平均进展无差异（-0.35；95%置信区间，-1.7至1.0；主要疗效结局）。锂组在PATA言语速率（P = 0.002）、非优势侧点击试验（P = 0.023）、脊髓小脑共济失调功能指数（P = 0.003）和综合小脑功能评分（P = 0.029）方面进展较小。
锂是安全且耐受性良好的，但在使用NESSCA测量时，对MJD/SCA3患者的疾病进展没有影响。次要结局的这种减缓值得进一步阐明。
