Hill Emily J, Goetz Christopher G, Stebbins Glenn T, Hagerman Randi, Ouyang Bichun, Hall Deborah A
Department of Neurology Baylor College of Medicine Houston Texas USA.
Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA.
Mov Disord Clin Pract. 2020 Mar 4;7(3):298-302. doi: 10.1002/mdc3.12919. eCollection 2020 Apr.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder characterized by intention tremor, cerebellar ataxia, and executive dysfunction in carriers of a CGG repeat expansion premutation (55-200 repeats) in the fragile X mental retardation 1 () gene. Given reports of poor insight in FXTAS, we postulated that patients with FXTAS would be less likely to exhibit placebo response.
To analyze placebo response from the first randomized controlled trial in FXTAS that evaluated cognitive and motor outcomes after 1 year of treatment with memantine.
Data from the placebo arm of the first randomized controlled trial in FXTAS were analyzed. There were 2 coprimary outcomes. Based on studies in Parkinson's disease, placebo responders were defined as individuals with an improvement of at least 50% in the coprimary outcomes. Improvements of 20% and 30% served as secondary cutoff values based on the suggested magnitude of placebo response in other movement disorders.
A total of 36 participants in the placebo group completed baseline and follow-up evaluations. The average age was 66 ± 7 years, and 60% were men. Average CGG repeat size was 86 ± 18. A total of 19 participants had stage 3 disease. Only 1 patient showed 50% improvement in both coprimary outcomes. At 30% and 20% improvement, there were 2 and 3 patients showing placebo response in the coprimary outcomes, respectively.
Patients with FXTAS exhibited low rates of placebo response in a randomized controlled trial. Further studies on the relationship between baseline insight and placebo responsivity are applicable to FXTAS and other disorders exhibiting cognitive impairment.
脆性X相关震颤/共济失调综合征（FXTAS）是一种神经退行性疾病，其特征为意向性震颤、小脑共济失调以及脆性X智力低下1（FMR1）基因中CGG重复序列扩展前突变（55 - 200次重复）携带者出现执行功能障碍。鉴于有报道称FXTAS患者洞察力较差，我们推测FXTAS患者出现安慰剂反应的可能性较小。
分析FXTAS首个随机对照试验中的安慰剂反应，该试验评估了美金刚治疗1年后的认知和运动结局。
对FXTAS首个随机对照试验的安慰剂组数据进行分析。有2个共同主要结局。基于帕金森病的研究，安慰剂反应者被定义为在共同主要结局中改善至少50%的个体。根据其他运动障碍中建议的安慰剂反应幅度，20%和30%的改善作为次要临界值。
安慰剂组共有36名参与者完成了基线和随访评估。平均年龄为66±7岁，60%为男性。平均CGG重复序列大小为86±18。共有19名参与者处于3期疾病。只有1例患者在两个共同主要结局中均有50%的改善。在30%和20%的改善水平上，分别有2例和3例患者在共同主要结局中表现出安慰剂反应。
在一项随机对照试验中，FXTAS患者的安慰剂反应率较低。关于基线洞察力与安慰剂反应性之间关系的进一步研究适用于FXTAS和其他表现出认知障碍的疾病。
