SCN1ANCT06504511
SCN1A Horizons A Natural History Study of SCN1A-related Epilepsies in the United Kingdom
An observational study of SCN1A and Dravet Syndrome, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
Trial summary
The aims of this prospective natural history study are to define the seizure, neuro-developmental, and behavioural characteristics of SCN1A-related epilepsies/Dravet syndrome in children and adults longitudinally over a period of three years. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- SCN1A, Dravet Syndrome, Epilepsy
- How many people
- 400 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Nov 2023to 1 Jun 2026
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Approximately 400 participants with a minimum of 2 years of follow-up are planned to be enrolled. Recruitment will be stratified according to the following age distribution: * 300 patients in the Comprehensive study arm (clinical and face-to-face neurodevelopmental assessments) * Approximately 60 participants aged 6 to 35 months * Approximately 80 participants aged 3 to 6 years inclusive * Approximately 100 participants aged 7 to 16 years inclusive * Approximately 60 participants aged 17 years and older * 100 patients in the Basic study arm (clinical and non-face-to-face neurodevelopmental assessments), in case the age specific quota in the Comprehensive study arm has been filled.
Who may be able to join
None listed.
Who cannot join
- Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or may affect the patient's ability to participate in the study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Hospital for Children
Glasgow, G51 4TF
Kirsty Hendry, PhD, 0141 4515888, kirsty.hendry@glasgow.ac.uk
About this study
The aims of this prospective natural history study are to define the seizure, neuro-developmental, and behavioural characteristics of SCN1A-related epilepsies/Dravet syndrome in children and adults longitudinally over a period of three years. In addition, this study will compare missense and truncating genotypes in terms of i) rates of change of countable convulsive seizures per month and ii) neurodevelopmental outcome and trajectories.
Read the detailed description
Our aim is to define the seizure, neurodevelopmental, and behavioural characteristics of SCN1A-related epilepsies/Dravet syndrome in children and adults longitudinally over a period of three years. In addition, this study will compare missense and truncating genotypes in terms of i) rates of change of countable convulsive seizures per month and ii) rate of change in neurodevelopmental outcomes over time. The investigators will therefore prospectively study the natural history of SCN1A-related epilepsies and Dravet syndrome in the UK. In order to explore established and novel treatments, including new medications, it is important to not only document seizure frequency but also behaviour, learning and motor function. Treatment interventions are key to prevent the neurodevelopmental comorbidities of Dravet syndrome; as such sensitive measures of disease progression and a clear prospective description of the natural history of the disease across the lifespan is required to know whether therapies are transformative.
Although the decline in neurodevelopmental profile and motor function in patients with SCN1A-related epilepsies/Dravet syndrome have been described, no large scale long-term, prospective studies of cognition and motor function have been conducted in SCN1A-related epilepsies/Dravet syndrome with established measures.
The SCN1A/Dravet syndrome natural history study will provide a platform to systematically collect longitudinal validated outcome measures for SCN1A variant-carrying patients across the UK. The study will prospectively assess changes in cognition, behaviour, and quality of life, as well as other co-morbidities.
A number of important questions relating to the natural history of SCN1A-related epilepsies/Dravet syndrome over the lifespan remain unanswered:
- It is not understood the precise neurodevelopmental profile and decline of individuals with SCN1A-related epilepsies over time and which factors might modify this?
- There are no reliable biomarkers that can inform disease severity or treatment planning
- What impact does the underlying genotype have on the neurodevelopmental outcome?
- Do clinical features such as the occurrence of repeated episodes of status epilepticus and/or contraindicated medication use worsen the neurodevelopmental outcome?
- What is the seizure burden across different ages and does treatment response change over the lifespan?
- There is a lack of understanding of the comorbidity profile that individuals with SCN1A-related epilepsies experience over the lifespan
- More information is required on the socio-economic impact SCN1A-related epilepsies have on affected individuals, families and society
- Conditions
- SCN1A, Dravet Syndrome, Epilepsy
- Keywords
- Epilepsy, SCN1A, Natural History, Developmental Outcome
- Medical subject headings
- Epilepsies, Myoclonic, Epilepsy
What is being measured
The primary outcome is the main question the study is designed to answer.
Countable convulsive seizures per month
A 4-week seizure diary will be completed by caregivers or participants (where they have capacity to do so) every 6 months.
Measured: Up to 3 year follow up
Bayley Scales of Infant and Toddler Development 4th UK Edition (Bayley-4)
Patients in the comprehensive arm who are <30 months of age will be administered the Bayley-4. Participants older than 30 months old may be administered the Bayely-4 if they are unable to access age-appropriate assessment. Standard scores range from 45-155 on each domain (cognitive, language \& motor). Growth Scale Values range from 428-559. Higher scores are indicative of higher developmental functioning.
Measured: Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. There is a planned 2-3 year follow up.
Wechsler Preschool and Primary Scale of Development 4th UK Edition (WPPSI-IV)
Patients in the comprehensive arm who are ≥2 years 5 months and ≤6 years of age will be administered the WPPSI-IV at Baseline. If the patient is unable to access the WPPSI-IV, they will be administered the Bayley-4 in addition to the WPPSI-IV at Baseline. Composite score for each domain ranges from 45-155. Composite full scale score ranges from 40-160. Higher scores are indicative of higher developmental functioning.
Measured: Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. There is a planned 2-3 year follow up.
Wechsler Intelligence Scale for Children 5th UK Edition (WISC-V)
Patients in the comprehensive arm aged 6 years to 16 years will be administered the WISC-V at baseline. If the patient is unable to access the WISC-V they will be administered the WPPSI-IV in addition to the WISC-V at Baseline. Participants will drop down to the Bayley-4 if they are unable to access the WPPSI-IV. Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. Composite score for each domain ranges from 45-155. Composite full scale score ranges from 40-160. Higher scores are indicative of higher developmental functioning.
Measured: Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. There is a planned 2-3 year follow up.
Wechsler Adult Intelligence Scale 4th UK Edition (WAIS-IV)
Patients in the comprehensive arm aged 16 years and older will be administered the WAIS-IV, 12-monthly. Composite score for each domain ranges from 50-150. Composite full scale score ranges from 40-160. Higher scores are indicative of higher developmental functioning.
Measured: Administration will occur 12-monthly. There is a planned 2-3 year follow up.
Vineland Adaptive Behaviour Scales - Third Edition
All patients in the comprehensive and basic arm will be administered the Vineland Adaptive Behaviour Scales - Third Edition, which will be completed by the caregiver. Raw scores range from 0-116. Standard scores range from 20-140. Growth Scale Values range from 10-197. Higher scores are indicative of higher developmental functioning.
Measured: Participants age <7 will have a Vineland assessment completed every 6 months, participants age 7 years and older will have a Vineland assessment completed every 12 months.
Secondary outcomes (4)
Occurrence and frequency of status epilepticus
Information obtained during 6-monthly standard of care clinical visit with Consultant Paediatric Neurologist for all patients.
Measured: Up to 3 year follow up
Grantham Score
A measure of physiochemical difference between amino acids. The score can range from 5-215, with a higher score indicative of more radical change in amino acid properties.
Measured: Baseline
Combined Annotation Dependent Depletion (CADD) score
Score of the deleteriousness of single nucleotide variants and insertion/deletion variants in the human genome. The score can range from 1-99, with higher values indicating more deleterious cases.
Measured: Baseline
Rare Exam Variant Ensemble Learner (REVEL) score
Predicts the pathogenicity of missense variants. The score can range from 0-1, with higher scores indicating a higher likelihood of the variant being disease-causing.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2024
- Study start20 Nov 2023
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCN1AStudies 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
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andreas Brunklaus, MD PhD, Principal investigator, NHS Greater Glasgow and Clyde
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06504511
- Sponsor's protocol ID
- GN20NE522P
- Other IDs
- 295069, 316675
- Status last verified
- Jul 2024
- First submitted
- 4 Jun 2024
- Last updated
- 16 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SCN1A Horizons A Natural History Study of SCN1A-related Epilepsies in the United Kingdom
- ClinicalTrials.gov ID
- NCT06504511
- Acronym / sponsor ID
- GN20NE522P
- Conditions
- SCN1A, Dravet Syndrome, Epilepsy
- Keywords
- Epilepsy, SCN1A, Natural History, Developmental Outcome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Study start
- 20 Nov 2023 (actual)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 16 Jul 2024 (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.
The aims of this prospective natural history study are to define the seizure, neuro-developmental, and behavioural characteristics of SCN1A-related epilepsies/Dravet syndrome in children and adults longitudinally over a period of three years. In addition, this study will compare missense and truncating genotypes in terms of i) rates of change of countable convulsive seizures per month and ii) neurodevelopmental outcome and trajectories.
Detailed description
Our aim is to define the seizure, neurodevelopmental, and behavioural characteristics of SCN1A-related epilepsies/Dravet syndrome in children and adults longitudinally over a period of three years. In addition, this study will compare missense and truncating genotypes in terms of i) rates of change of countable convulsive seizures per month and ii) rate of change in neurodevelopmental outcomes over time. The investigators will therefore prospectively study the natural history of SCN1A-related epilepsies and Dravet syndrome in the UK. In order to explore established and novel treatments, including new medications, it is important to not only document seizure frequency but also behaviour, learning and motor function. Treatment interventions are key to prevent the neurodevelopmental comorbidities of Dravet syndrome; as such sensitive measures of disease progression and a clear prospective description of the natural history of the disease across the lifespan is required to know whether therapies are transformative.
Although the decline in neurodevelopmental profile and motor function in patients with SCN1A-related epilepsies/Dravet syndrome have been described, no large scale long-term, prospective studies of cognition and motor function have been conducted in SCN1A-related epilepsies/Dravet syndrome with established measures.
The SCN1A/Dravet syndrome natural history study will provide a platform to systematically collect longitudinal validated outcome measures for SCN1A variant-carrying patients across the UK. The study will prospectively assess changes in cognition, behaviour, and quality of life, as well as other co-morbidities.
A number of important questions relating to the natural history of SCN1A-related epilepsies/Dravet syndrome over the lifespan remain unanswered:
- It is not understood the precise neurodevelopmental profile and decline of individuals with SCN1A-related epilepsies over time and which factors might modify this?
- There are no reliable biomarkers that can inform disease severity or treatment planning
- What impact does the underlying genotype have on the neurodevelopmental outcome?
- Do clinical features such as the occurrence of repeated episodes of status epilepticus and/or contraindicated medication use worsen the neurodevelopmental outcome?
- What is the seizure burden across different ages and does treatment response change over the lifespan?
- There is a lack of understanding of the comorbidity profile that individuals with SCN1A-related epilepsies experience over the lifespan
- More information is required on the socio-economic impact SCN1A-related epilepsies have on affected individuals, families and society
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Approximately 400 participants with a minimum of 2 years of follow-up are planned to be enrolled. Recruitment will be stratified according to the following age distribution: * 300 patients in the Comprehensive study arm (clinical and face-to-face neurodevelopmental assessments) * Approximately 60 participants aged 6 to 35 months * Approximately 80 participants aged 3 to 6 years inclusive * Approximately 100 participants aged 7 to 16 years inclusive * Approximately 60 participants aged 17 years and older * 100 patients in the Basic study arm (clinical and non-face-to-face neurodevelopmental assessments), in case the age specific quota in the Comprehensive study arm has been filled.
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or may affect the patient's ability to participate in the study.
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
Countable convulsive seizures per month
Time frame: Up to 3 year follow up
A 4-week seizure diary will be completed by caregivers or participants (where they have capacity to do so) every 6 months.
Bayley Scales of Infant and Toddler Development 4th UK Edition (Bayley-4)
Time frame: Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. There is a planned 2-3 year follow up.
Patients in the comprehensive arm who are <30 months of age will be administered the Bayley-4. Participants older than 30 months old may be administered the Bayely-4 if they are unable to access age-appropriate assessment. Standard scores range from 45-155 on each domain (cognitive, language \& motor). Growth Scale Values range from 428-559. Higher scores are indicative of higher developmental functioning.
Wechsler Preschool and Primary Scale of Development 4th UK Edition (WPPSI-IV)
Time frame: Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. There is a planned 2-3 year follow up.
Patients in the comprehensive arm who are ≥2 years 5 months and ≤6 years of age will be administered the WPPSI-IV at Baseline. If the patient is unable to access the WPPSI-IV, they will be administered the Bayley-4 in addition to the WPPSI-IV at Baseline. Composite score for each domain ranges from 45-155. Composite full scale score ranges from 40-160. Higher scores are indicative of higher developmental functioning.
Wechsler Intelligence Scale for Children 5th UK Edition (WISC-V)
Time frame: Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. There is a planned 2-3 year follow up.
Patients in the comprehensive arm aged 6 years to 16 years will be administered the WISC-V at baseline. If the patient is unable to access the WISC-V they will be administered the WPPSI-IV in addition to the WISC-V at Baseline. Participants will drop down to the Bayley-4 if they are unable to access the WPPSI-IV. Administration will occur 6-monthly for patients <7 years old and 12-monthly for patients 7 years and older. Composite score for each domain ranges from 45-155. Composite full scale score ranges from 40-160. Higher scores are indicative of higher developmental functioning.
Wechsler Adult Intelligence Scale 4th UK Edition (WAIS-IV)
Time frame: Administration will occur 12-monthly. There is a planned 2-3 year follow up.
Patients in the comprehensive arm aged 16 years and older will be administered the WAIS-IV, 12-monthly. Composite score for each domain ranges from 50-150. Composite full scale score ranges from 40-160. Higher scores are indicative of higher developmental functioning.
Vineland Adaptive Behaviour Scales - Third Edition
Time frame: Participants age <7 will have a Vineland assessment completed every 6 months, participants age 7 years and older will have a Vineland assessment completed every 12 months.
All patients in the comprehensive and basic arm will be administered the Vineland Adaptive Behaviour Scales - Third Edition, which will be completed by the caregiver. Raw scores range from 0-116. Standard scores range from 20-140. Growth Scale Values range from 10-197. Higher scores are indicative of higher developmental functioning.
4 secondary outcomes
Occurrence and frequency of status epilepticus
Time frame: Up to 3 year follow up
Grantham Score
Time frame: Baseline
Combined Annotation Dependent Depletion (CADD) score
Time frame: Baseline
Rare Exam Variant Ensemble Learner (REVEL) score
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2024.
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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.
Andreas Brunklaus, MD PhD principal investigator
NHS Greater Glasgow and Clyde
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SCN1A and Dravet Syndrome, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
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 0 inclusion and 1 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 16 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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 Kirsty Hendry, PhD (0141 451 5888, SCN1AHorizons@glasgow.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Countable convulsive seizures per month (time frame: Up to 3 year follow up). The study lists 6 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 16 Jul 2024.