Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex (PREVeNT Trial) A Randomized, Double-blind, Placebo-controlled Seizure Prevention Clinical Trial for Infants With TSC
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 84
- 试验地点
- 13
- 主要终点
- Cognitive Assessment Scores and Developmental Impact
研究概览
简要总结
Study design is a Phase IIb prospective multi-center, randomized, placebo-controlled, double-blind clinical trial. The goal will be to enroll 80 infants with Tuberous Sclerosis Complex who are less than 6 months of age prior to the onset of their first seizure
详细描述
The central hypothesis of this Phase IIb trial is that early identification of electroencephalography (EEG) biomarkers and early treatment versus delayed treatment with vigabatrin in infants with tuberous sclerosis complex (TSC) will have a positive impact on developmental outcomes at 24 months of age. It would also prevent or lower the risk of developing infantile spasms and refractory seizures. This preventative approach would be expected to result in more favorable long-term cognitive, behavioral, developmental and psychiatric outcomes and significantly improve overall quality of life. It is a randomized, double-blind, placebo-controlled clinical trial design. Successful completion of this trial will also advance the field by demonstrating the value of systematic surveillance with EEG in asymptomatic infants with TSC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Day 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •less than or equal to 6 months of age
- •No history of seizures or infantile spasms, or evidence of subclinical electrographic seizures on a previous video EEG
- •Meet genetic or clinical diagnostic criteria for TSC, the latter based on current recommendations for diagnostic evaluation, such as physical exam, neuroimaging, echocardiogram
排除标准
- •Is greater than 6 months of age
- •Has not been diagnosed with TSC
- •History of seizures or infantile spasms, or evidence of subclinical electrographic seizures on a previous video EEG
- •Has received any anticonvulsant medication including vigabatrin, other anti-seizure therapeutic agent including cannabidiol
- •Has received an oral mTOR inhibitor such as everolimus or sirolimus
- •Has taken an investigational drug, including but not limited to cannabidiol, as part of a research study 30 days prior to enrollment, or plans on taking an investigational drug at any time during the duration of the study
- •Is currently enrolled, or plans on enrolling at any time during the duration of the study, in an experimental behavioral early intervention study
- •Has a history of being born prematurely (born less than <30 weeks gestation at the time of delivery)
研究组 & 干预措施
Delayed Vigabatrin (Placebo)
Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
干预措施: Early Vigabatrin (Drug)
Delayed Vigabatrin (Placebo)
Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
干预措施: Delayed Vigabatrin (Placebo) (Drug)
Early Vigabatrin
Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
干预措施: Early Vigabatrin (Drug)
结局指标
主要结局
Cognitive Assessment Scores and Developmental Impact
时间窗: 24 months
The primary outcome measure will be the standardized Cognitive scale scores on the Bayley Scales of Infant and Toddler Development- Third Edition at 24 months. The Cognitive scale Composite score is a standard score derived from the observed and elicited performance of the child on cognitive assessment tasks, with a mean of 100 and standard deviation of 10. The range for the Cognitive scale Composite score is 55 to 145. The score is calculated using standard procedures available in the manual for this measure. A higher score is considered better performance. The Bayley Scales of Infant and Toddler Development at 24 months will be used for the data analysis and to compare the developmental impact of early versus delayed treatment with vigabatrin.
次要结局
- Count of Participants With Drug Resistant Epilepsy at 24 Months of Age.(24 months)
- Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment(12 months, 24 months and 36 months)
- Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.(24 months)
- Time to the Subject's First Clinical Seizure From Randomization(24 months)
- Number of Subjects With Vigabatrin Related Adverse Events and Severe Adverse Events(24 months)
- EEG Biomarker for Developing Epilepsy(24 months)
- Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment(24 months and 36 months)
研究者
Martina Bebin
Professor of Neurology and Pediatrics
University of Alabama at Birmingham