Clinical trial NCT06082999: Gene-STEPS: Shortening Time of Evaluation in Paediatric Epilepsy Services
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Epilepsy
Keywords: Epilepsy
Whole Genome Sequencing
Genetics
Paediatric
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Murdoch Childrens Research Institute
name: The Hospital for Sick Children
name: Boston Children's Hospital
First posted: 2023-10-13
Enrollment: 300
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with epilepsy onset under 12 months of age presenting to an epilepsy service. This is an international multi-centre collaborative study with GOSH as the UK sponsor.

Brief summary: Overall, this observational cohort study aims too:

1. Implement rapid trio WGS for all children presenting to our health systems with epilepsy onset under 12 months of age.
2. 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.
3. Assess the impact of early genetic diagnosis on epilepsy, developmental, and health economic outcomes through formal longitudinal assessments of all children enrolled.

Detailed description: 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:

1. Implement rapid trio WGS for all children presenting to our health systems with epilepsy onset under 12 months of age.
2. 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.
3. Assess the impact of early genetic diagnosis on epilepsy, developmental, and health economic outcomes through formal longitudinal assessments of all children enrolled.

Eligibility criteria: Inclusion Criteria:

• Children under 12 months of age presenting with epilepsy.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Feasibility of rapid genome sequencing in infantile epilepsy
timeFrame: Within three weeks of sample collection
measure: The Diagnostic Yield of rapid genome sequencing in infantile epilepsy
timeFrame: Within three weeks of sample collection
measure: The immediate clinical utility of rapid genome sequencing in infantile epilepsy
timeFrame: Within one month of genetic result
Secondary outcomes:
measure: The impact of early genetic diagnosis on developmental outcomes - Bayley 4 - Scales of Infant and Toddler Development.
timeFrame: At Recruitment, 12 and 30 months chronological age
measure: The impact of early genetic diagnosis on developmental outcomes - Vineland Adaptive Behaviour Scales, Third Edition.
timeFrame: At Recruitment, 12 and 30 months chronological age
measure: The impact of early genetic diagnosis on developmental outcomes - Gross Motor Function Classification System (GMFCS)
timeFrame: At Recruitment, 12 and 30 months chronological age
measure: The impact of early genetic diagnosis on developmental outcomes - Paediatric Quality of Life Scale (PedsQL™) Infant Scales
timeFrame: At Recruitment, 12 and 30 months chronological age
measure: The impact of early genetic diagnosis on developmental outcomes - Parenting Stress Index, Fourth Edition Short Form
timeFrame: At Recruitment, 12 and 30 months chronological age
measure: The impact of early genetic diagnosis on epilepsy
timeFrame: 12 months and 30 months chronological age. The clinical dataset will also be retrieved at recruitment.
measure: The views and experiences of parents offered rapid genomic sequencing for diagnosis of their child
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Parkville
country: Australia
facility: Murdoch Childrens Research Institute
state: Victoria
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: London
country: United Kingdom
facility: UCL Great Ormond Street Institute of Child Health
Study officials:
affiliation: UCL Great Ormond Street Institute of Child Health
name: Amy McTague
role: PRINCIPAL_INVESTIGATOR
References: