SCN1A Horizons A Natural History Study of SCN1A-related Epilepsies in the United Kingdom
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorNHS Greater Glasgow and Clyde
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
None
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
No trial groups listed
Trial outcomes
Primary outcomes
1
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.
Time frame
Up to 3 year follow up2
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.
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.3
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.
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.4
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.
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.Secondary outcomes
1
Occurrence and frequency of status epilepticus
Information obtained during 6-monthly standard of care clinical visit with Consultant Paediatric Neurologist for all patients.
Time frame
Up to 3 year follow up2
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.
Time frame
Baseline3
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.
Time frame
Baseline4
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.
Time frame
BaselineSponsors and contacts
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Source ClinicalTrials.gov