SCN1A Horizons A Natural History Study of SCN1A-related Epilepsies in the United Kingdom
NCT Number: NCT06504511
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: SCN1A|Dravet Syndrome|Epilepsy
Sponsor: NHS Greater Glasgow and Clyde
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 400
Study Design: Observational Model: |Time Perspective: p
Start Date: 2023-11-20
Completion Date: 2026-06-01
Locations: Royal Hospital for Children, Glasgow, G51 4TF, United Kingdom

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. 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.

Primary Outcome Measures: 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., 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., 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., 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., 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., 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., 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 Outcome Measures: Occurrence and frequency of status epilepticus, Information obtained during 6-monthly standard of care clinical visit with Consultant Paediatric Neurologist for all patients., 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., 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., 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., Baseline