SCN1A Horizons A Natural History Study of SCN1A-related Epilepsies in the United Kingdom

NCT06504511 | Recruiting

• 3 other identifiers: GN20NE522P295069316675
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

SCN1A; Dravet Syndrome; Epilepsy

Keywords

Epilepsy; SCN1A; Natural History; Developmental Outcome

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• Occurrence and frequency of status epilepticus

  Up to 3 year follow up

• Grantham Score

  Baseline

• Combined Annotation Dependent Depletion (CADD) score

  Baseline

• Rare Exam Variant Ensemble Learner (REVEL) score

  Baseline

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• Patient and/or legally authorised representative must be willing and able to give informed consent/assent for participation in the study.
• Patient and parent/caregiver are willing and able (in the Investigator's opinion) to comply with all study requirements (including ability and willingness to comply with virtual visits).
• Participant has a confirmed pathogenic (class 5) or likely pathogenic (class 4. SCN1A variant, as demonstrated by genetic testing.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead

Study Sites (1)

Royal Hospital for Children

Glasgow, G51 4TF, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

2x 4ml EDTA blood sample at baseline visit.

MeSH Terms

Conditions

Epilepsies, Myoclonic; Epilepsy

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Andreas Brunklaus, MD PhD

  NHS Greater Glasgow & Clyde

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kirsty Hendry, PhD

CONTACT

0141 451 5888; SCN1AHorizons@glasgow.ac.uk

Andreas Brunklaus, MD PhD

CONTACT

0141 451 5888; andreas.brunklaus@glasgow.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: July 16, 2024
• Study Start: November 20, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

GB (1)