EpilepsyGene-STEPSNCT06082999
Gene-STEPS: Shortening Time of Evaluation in Paediatric Epilepsy Services
An observational study of Epilepsy, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 4 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 12 months
- Conditions the study is for
- Epilepsy
- How many people
- 300 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 1 Sep 2021to Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 12 months
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- Children under 12 months of age presenting with epilepsy.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Ann Poduri, Dr, Annapurna.Poduri@childrens.harvard.edu
Australia1 site, 1 recruiting
- Recruiting
Murdoch Childrens Research Institute
Parkville, Victoria, 3052
Katherine Howell, Dr, Katherine.Howell@rch.org.au
Canada1 site, 1 recruiting
- Recruiting
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Gregory Costain, Dr, gregory.costain@sickkids.ca
United Kingdom1 site, 1 recruiting
- Recruiting
UCL Great Ormond Street Institute of Child Health
London, WC1N 1DZ
Amy McTague, Dr, a.mctague@ucl.ac.uk
About this study
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
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.
Read the 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:
- 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.
- Conditions
- Epilepsy
- Keywords
- Epilepsy, Whole Genome Sequencing, Genetics, Paediatric
- Medical subject headings
- Epilepsy
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of rapid genome sequencing in infantile epilepsy
Feasibility is measured as the turnaround for participants, from both sample collection and seizure onset to GS result.
Measured: Within three weeks of sample collection
The Diagnostic Yield of rapid genome sequencing in infantile epilepsy
The diagnostic yield is measured as the number of patients who receive a genetic diagnosis.
Measured: Within three weeks of sample collection
The immediate clinical utility of rapid genome sequencing in infantile epilepsy
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.
Measured: Within one month of genetic result
Secondary outcomes (7)
The impact of early genetic diagnosis on developmental outcomes - Bayley 4 - Scales of Infant and Toddler Development.
Bayley-4 items are scored 2 points for mastery of skill, 1 point for emerging skill and 0 points if skill is not present. Higher scores are, therefore, indicative of more advanced developmental abilities. Subtest standard scores range from 1 to 19, have a mean of 10 and a standard deviation of 3 (Bayley \& Alyward, 2019).
Measured: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on developmental outcomes - Vineland Adaptive Behaviour Scales, Third Edition.
The Vineland 3 generates five major domain composite scores: communication, daily living skills, socialisation, adaptive behaviour composite and motor skills, as well as a maladaptive score. Domain scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low-to-low, and indicate the patient has a significant skill deficit when compared with similarly aged peers. This is especially true for a domain score below 70. Maladaptive behavior scores up to 17 are considered average, scores of 18 to 20 are considered elevated and scores greater than 21 are considered clinically significant indicating a need for treatment intervention.
Measured: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on developmental outcomes - Gross Motor Function Classification System (GMFCS)
The GMFCS is a standardised classification of functional motor abilities in children with cerebral palsy. Children are assigned a GMFCS level of 1-V according to motor functioning abilities. Level I represents the highest level of gross motor function and level V the lowest.
Measured: 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
The PedsQL™ Infant Scales are a generic health related quality of life instrument specifically for healthy and ill infants ages 1-24 months. The PedsQL Infant Scales encompasses 5 scales: Physical functioning, physical symptoms, emotional functioning, social functioning and cognitive functioning. The Total Scale Score is computed as the sum of all items on the PedsQL™. Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL.
Measured: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on developmental outcomes - Parenting Stress Index, Fourth Edition Short Form
The PSI-4 SF has thirty-six items are divided into three domains: Parental Distress (PD), Parent-Child Dysfunctional Interaction (P-CDI), and Difficult Child (DC), which combine to form a Total Stress scale. Percentile scoring: Between 16%-84% = Normal ranges of stress. Between 85%-89% = High levels of stress. Greater than or equal to 90% = Clinically significant.
Measured: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on epilepsy
Clinical Dataset \& Seizure diary 4 weeks prior to visit
Measured: 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
Qualitative interviews will be utilised to ascertain parents experiences of receiving the result, the impact of the result, and their hopes and concerns for the future. Parents who decline to participate will be asked about their decision not to take part in the study and have genome sequencing and suggestions for improving counselling and information.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2023
- Study start1 Sep 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Murdoch Childrens Research Institute, The Hospital for Sick Children, Boston Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Amy McTague, Principal investigator, UCL Great Ormond Street Institute of Child Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06082999
- Sponsor's protocol ID
- 20NM24
- Acronym
- Gene-STEPS
- Status last verified
- Aug 2023
- First submitted
- 31 Aug 2023
- Last updated
- 13 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06082999
- Acronym / sponsor ID
- Gene-STEPS / 20NM24
- Conditions
- Epilepsy
- Keywords
- Epilepsy, Whole Genome Sequencing, Genetics, Paediatric
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Murdoch Childrens Research Institute, The Hospital for Sick Children, Boston Children's Hospital
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 13 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (1 listed)
- Children under 12 months of age presenting with epilepsy.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Feasibility of rapid genome sequencing in infantile epilepsy
Time frame: 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
Time frame: 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
Time frame: 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.
7 secondary outcomes
The impact of early genetic diagnosis on developmental outcomes - Bayley 4 - Scales of Infant and Toddler Development.
Time frame: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on developmental outcomes - Vineland Adaptive Behaviour Scales, Third Edition.
Time frame: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on developmental outcomes - Gross Motor Function Classification System (GMFCS)
Time frame: 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
Time frame: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on developmental outcomes - Parenting Stress Index, Fourth Edition Short Form
Time frame: At Recruitment, 12 and 30 months chronological age
The impact of early genetic diagnosis on epilepsy
Time frame: 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
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Epilepsy
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy McTague principal investigator
UCL Great Ormond Street Institute of Child Health
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Australia, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amy McTague, Dr (02039783678, a.mctague@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of rapid genome sequencing in infantile epilepsy (time frame: Within three weeks of sample collection). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2023.