Preventing Epilepsy using Vigabatrin in Infants with Tuberous Sclerosis Complex

 描述(由申请人提供)：预防试验是一项IIb期随机、双盲、安慰剂对照试验，在患有结节性硬化症(TSC)的婴儿中使用Vigabatrin。这项研究的主要目标是基于Bayley-III的认知评估分数，在24个月龄时早期和延迟使用Vigabatrin治疗对发育的影响。次要研究目标将集中在早期和延迟使用Vigabatrin治疗在临床预防癫痫方面的有效性以及24个月大时耐药癫痫的患病率。此外，早期和延迟Vigabatrin治疗对接受性沟通、表达沟通、精细和粗大运动技能以及患自闭症谱系障碍(ASD)的风险的影响。这个次级目标的结果测量将是24个月时Bayley-III、Vineland-II、Beery视觉运动整合(VMI)、皮博迪图片词汇测试(PPVT)、区分能力量表II(DAS-II)和ADOS2的子域分数。另外的探索性分析将在36个月时完成，以了解24个月时观察到的变化与36个月时观察到的变化一致，并表明长期结果。此外，还将进行分析以确定Vigabatrin作为TSC研究人群中癫痫发作的预防性治疗的安全性。这项研究还将确认使用脑电生物标记物来识别TSC婴儿患癫痫的风险的可行性。由于产前超声等技术的进步，TSC的早期诊断是可能的，而且由于非神经系统的发现，现在通常在癫痫发作之前进行产前或早期婴儿诊断[Datta等人。2008年)。因此，有一个适当的 在临床癫痫发作和随后的癫痫发作之前识别高危患者并启动潜在的抗癫痫治疗的机会之窗。药物难治性癫痫和相关的智能障碍、自闭症谱系障碍和精神健康障碍在该人群中的流行率已有很好的记录，[Chu-Shore等人，2010]，这证明在TSC患者的症状前阶段开始治疗具有潜在的副作用。这一建议的中心假设是，早期识别脑电生物标志物并对患有TSC的婴儿进行症状前治疗可以预防或降低发生婴儿痉挛和/或难治性癫痫发作的风险。这种预防性的方法将促进更有利的认知、行为、发育和精神结果。

 DESCRIPTION (provided by applicant): The PREVeNT Trial is a phase IIb randomized double-blind placebo-controlled trial with vigabatrin in infants with Tuberous Sclerosis Complex (TSC). The primary objective of the study is the developmental impact of early versus delayed treatment with vigabatrin at 24 months of age based on the cognitive assessment score of the Bayley-III. The secondary study objectives will focus on the effectiveness of early versus delayed treatment with vigabatrin in clinical seizure prevention and the prevalence of drug resistant epilepsy by the age of 24 months. Also, the impact of early versus delayed vigabatrin treatment on receptive communication, expressive communication, fine and gross motor skills, and risk of autism spectrum disorders (ASD). The outcome measures for this secondary objective will be subdomain scores of the Bayley-III, Vineland-II, Beery Visual Motor Integration (VMI), Peabody Picture Vocabulary Test (PPVT), Differential Ability Scales-II (DAS-II) and ADOS2 at 24 months. Additional exploratory analysis will be completed at 36 months to access changes observed at 24 months are consistent with those seen at 36 months and indicative of long-term outcome. In addition, analysis will be done to determine the safety of vigabatrin as a preventative treatment for seizures in this TSC study population. The study will also confirm the feasibility of using EEG biomarkers to identify TSC infants at risk for developing epilepsy. The early diagnosis of TSC is possible because of the advances in technology such as prenatal ultrasound and often the diagnosis is now made prenatally or in early infancy before the onset of epilepsy due to non- neurological findings [Datta et al. 2008]. As a result there is an appropriate window of opportunity to identify at- risk patients and initiate potential antiepileptogenic treatment prior to the onset of clinical seizures and subsequent epilepsy. The prevalence of medically-refractory epilepsy and associated intellectual impairment, autism spectrum disorders, and mental health disabilities in this population is well documented, [Chu-Shore et al 2010], justifying the initiation of therapy with potential side effects in a presymptomatic stage in TSC patients. The central hypothesis of this proposal is that early identification of EEG biomarkers and presymptomatic treatment with vigabatrin in infants with TSC can prevent or lower the risk of developing infantile spasms and/or refractory seizures. This preventative approach would promote more favorable cognitive, behavioral, developmental, and psychiatric outcomes.