Gene-STEPS: Shortening Time of Evaluation in Paediatric Epilepsy Services: a Multi-centre Prospective Evaluation of the Impact of Early Genetic Diagnosis on Patient Outcomes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 4
- 主要终点
- Feasibility of rapid genome sequencing in infantile epilepsy
研究概览
简要总结
Overall, this observational cohort study aims too:
- Implement rapid trio WGS for all children presenting to our health systems with epilepsy onset under 12 months of age.
- Utilize electronic healthcare records and research databases to unite phenotypic and genomic data and to create a "virtual" registry across all institutions that will promote ongoing discovery.
- Assess the impact of early genetic diagnosis on epilepsy, developmental, and health economic outcomes through formal longitudinal assessments of all children enrolled.
详细描述
In the past decade, the genomic revolution has led to the identification of underlying genetic aetiologies for childhood epilepsy, in the form of monogenic disorders affecting ion channels, neurotransmitter receptors, synaptic proteins, and other families of proteins. In a growing number of cases, the specific genetic diagnosis informs prognosis and genetic counselling, leads to the opportunity to participate in natural history studies, and even to changes in treatment that, to date anecdotally, may change outcomes in seizures and in neurodevelopment. However, a major challenge in clinical practice is that early intervention requires early diagnosis.
Currently the diagnostic odyssey in early-onset epilepsy is long and arduous for patients and their families. The timing and nature of genetic testing for such patients varies widely within and across countries and institutions. Our collective expertise includes epilepsy genetics research, genomic research, clinical epilepsy, clinical trials, and team science across four leading paediatric institutions in the IPCHiP Consortium: Boston Children's Hospital (US), Great Ormond Street Hospital and UCL Great Ormond Street Institute of Child Health (UK), Royal Children's Hospital Melbourne and Murdoch Children's Research Institute (Australia), and The Hospital for Sick Children ("Sick Kids", Canada). Each of our institutions has a proven track record of discovery and translation to patients, and our combined efforts in epilepsy will set a new standard for multi-institutional research, data sharing, and improvement. To investigate our hypothesis that rapid genetic diagnosis and tailored management could improve outcomes, we propose a novel approach to streamline and accelerate diagnostics in these severely affected children.
Overall, this observational cohort study aims too:
- Implement rapid trio WGS for all children presenting to our health systems with epilepsy onset under 12 months of age.
- Utilize electronic healthcare records and research databases to unite phenotypic and genomic data and to create a "virtual" registry across all institutions that will promote ongoing discovery.
- Assess the impact of early genetic diagnosis on epilepsy, developmental, and health economic outcomes through formal longitudinal assessments of all children enrolled.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children under 12 months of age presenting with epilepsy.
排除标准
- •Simple febrile seizures.
- •Acute or remote symptomatic seizures due to sepsis, haemorrhage, cerebral infarction, hypoxic ischaemic encephalopathy or non-accidental injury.
- •Structural malformations of the brain where the likely genetic cause is known such as tuberous sclerosis or lissencephaly.
结局指标
主要结局
Feasibility of rapid genome sequencing in infantile epilepsy
时间窗: Within three weeks of sample collection
Feasibility is measured as the turnaround for participants, from both sample collection and seizure onset to GS result.
The Diagnostic Yield of rapid genome sequencing in infantile epilepsy
时间窗: Within three weeks of sample collection
The diagnostic yield is measured as the number of patients who receive a genetic diagnosis.
The immediate clinical utility of rapid genome sequencing in infantile epilepsy
时间窗: Within one month of genetic result
Clinical utility is measured as actual influence on treatment, potential for precision therapy, additional investigation indicated or avoided, additional prognostic information, influence on goals of care, or influence on genetic counselling (beyond recurrence risk). These are measured using The Clinician-reported Genetic testing Utility InDEx (C-GUIDE; Hayeems et al., 2022), as well as clinical data abstracted from health care records.
次要结局
- The impact of early genetic diagnosis on developmental outcomes - Parenting Stress Index, Fourth Edition Short Form(At Recruitment, 12 and 30 months chronological age)
- The impact of early genetic diagnosis on developmental outcomes - Vineland Adaptive Behaviour Scales, Third Edition.(At Recruitment, 12 and 30 months chronological age)
- The impact of early genetic diagnosis on developmental outcomes - Gross Motor Function Classification System (GMFCS)(At Recruitment, 12 and 30 months chronological age)
- The impact of early genetic diagnosis on developmental outcomes - Bayley 4 - Scales of Infant and Toddler Development.(At Recruitment, 12 and 30 months chronological age)
- The impact of early genetic diagnosis on developmental outcomes - Paediatric Quality of Life Scale (PedsQL™) Infant Scales(At Recruitment, 12 and 30 months chronological age)
- The impact of early genetic diagnosis on epilepsy(12 months and 30 months chronological age. The clinical dataset will also be retrieved at recruitment.)
- The views and experiences of parents offered rapid genomic sequencing for diagnosis of their child(For participating parents: 3-4 weeks and then 6 months after receiving GS result. For non-participating parents: 3 months after deciding not to participate.)