Long-term, Prospective Study Evaluating Clinical and Molecular Biomarkers of Epileptogenesis in a Genetic Model of Epilepsy - Tuberous Sclerosis Complex
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 100
- 试验地点
- 9
- 主要终点
- number of patients with epilepsy
研究概览
简要总结
The primary objective of clinical part of EPISTOP project is to identify the clinical and molecular biomarkers of epileptogenesis in a prospective clinical study of patients with TSC.
Secondary objective of the clinical part of EPISTOP is to compare the effects of standard antiepileptic treatment in patients diagnosed as having epilepsy after clinical seizures vs after electroencephalographic epileptiform discharges, in a randomized trial in TSC patients.
详细描述
Overview of study design This is a prospective study of epileptogenesis in TSC infants. In control subjects only one blood sampling will be performed and those infants will not be observed prospectively.
The study consists of two phases: (1) prospective tracking of epileptogenesis by means of serial vEEG recordings; (2) treatment of epilepsy diagnosed after clinical or after electroencephalographic epileptiform discharges.
All patients enrolled in the study will participate in the first phase. The second phase will concern only the children with epilepsy with electroencephalographic epileptiform discharges and/or clinical seizures, whose parents/caregivers will give consent for the randomized part of the project.
At baseline, all patients will undergo neuroimaging examination by means of MRI, a battery of neuropsychological tests, blood biomarker sampling, and the review of medical history of the patient and the family.
Epileptogenesis in TSC infants will be tracked by means of serial vEEG recordings. In children with diagnosed epilepsy, standard therapy with recommended first line antiepileptic drug will be given. Children with clinical seizures, either noticed by a caregiver, or a treating neurologist or recorded on video during vEEG will be immediately diagnosed as having epilepsy. Infants that have epileptiform discharges on vEEG and no clinical seizures, if their parents/caregivers give consent, will enter the randomized part of the study. Those children will be randomized into two groups: group A will be diagnosed as having epilepsy after subclinical (electroencephalographic) epileptiform discharges, and the patients in group B will be diagnosed as epileptic after clinical seizures appear. All infants diagnosed with epilepsy will receive standard therapy with recommended first line antiepileptic drug starting from the day of diagnosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- — 至 4 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria for TSC patients:
- •male or female infants with a definite diagnosis of TSC (Roach criteria; Roach 1998 or DNA confirmed),
- •age up to 4 months at the moment of enrolment,
- •no clinical seizures seen by caregivers or on baseline videoEEG recording,
- •written informed consent of caregivers. It is possible to give consent for the observational part of the study only. In this case, the child will not enter the randomized part of the study.
- •Inclusion criteria for the control group:
- •male or female infants who have undergone routine MRI for reasons other than epilepsy and brain tumor or cortical defects,
- •age up to 24 months at the moment of study entry,
- •written informed consent of caregivers.
排除标准
- •Exclusion criteria for TSC patients:
- •any type of seizures observed till baseline visit,
- •antiepileptic treatment at or prior to study entry,
- •contraindications to MRI,
- •any severe and/or uncontrolled medical condition that is considered by the investigator as possibly affecting the EPISTOP analyses or procedures.
- •Exclusion criteria for the control group:
- •any sign or symptom suggesting TSC diagnosis,
- •any type of seizures observed at study entry,
- •antiepileptic treatment at study entry,
- •history of seizures, with the exception of febrile seizures,
- •any severe and/or uncontrolled medical condition that is considered by the investigator as possibly affecting the EPISTOP analyses or procedures.
结局指标
主要结局
number of patients with epilepsy
时间窗: at 24 month of life
Full analysis set comprises all patients participating in the study, including the control group. This set will be divided into subsets: control group, TSC patients with epilepsy, and TSC patients with no epilepsy. Among TSC patients with epilepsy, patients with well-controlled seizures and patients with drug-resistant epilepsy will be identified. In full analysis set the blood biomarkers will be analysed. Clinical analysis set will comprise of all TSC infants enrolled in the study and the clinical biomarkers of epileptogenesis (neuroimaging, vEEG, data from medical history) will be analysed in this set. Treatment analysis set will comprise of infants participating in the randomized part of the study and the efficacy of antiepileptic treatment in respect to the point of epilepsy diagnosis (electroencephalographic epileptiform discharges onset in group A and clinical seizures onset in group B) will be assessed in this set.
次要结局
未报告次要终点
研究者
Sergiusz Jozwiak
MD, PhD
Children's Memorial Health Institute, Poland