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.
This study focuses on the developmental impact of early vigabatrin treatment in infants with Tuberous Sclerosis Complex who are at risk of developing epilepsy. Also, the study aims to determine the effectiveness of early vigabatrin treatment in clinical seizure prevention and its impact on the development of drug resistant epilepsy at 24months of age. This is the first seizure prevention trial in patients with TSC in the United States.
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