背景:脊髓小脑性共济失调3型(SCA3)是一种神经退行性疾病,其特征是共济失调和非共济失调特征日益恶化,对患者生活质量产生负面影响。本研究旨在正式评估口服海藻糖对SCA3患者是否有效。
方法:在这种双盲中,随机对照试验,SCA3患者接受100克口服海藻糖或30克麦芽糖,以改善共济失调的严重程度超过六个月。我们还测量了其他临床(非共济失调),患者报告(生活质量,动机),和安全端点。使用双向ANOVA进行了计划外的中期分析,以分析时间之间的相互作用(基线,3个月,6个月)和干预(海藻糖与安慰剂)。
结果:15名参与者(海藻糖=7vs.安慰剂=8)在中期分析时完成研究。对共济失调严重程度没有交互作用,现有数据表明,在一项为期6个月的试验中,估计需要132例(每臂66例)SCA3患者的样本量来证明变化.执行功能存在显著的交互效应(2=0.28-0.43)。安全性数据表明100g口服海藻糖具有良好的耐受性。
结论:由于招募速度缓慢,我们进行了计划外的中期分析。新的估计样本量被认为是不可行的,导致临床试验提前终止。在这个小小的,SCA3患者的当前样本,与安慰剂相比,100g口服海藻糖对共济失调严重程度没有差异影响。有趣的是,我们的发现可能提示执行功能有所改善.未来的努力需要一个庞大的多国,多中心研究研究海藻糖的潜在作用。
BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients\' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients.
METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo).
RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated.
CONCLUSIONS: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.