Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies
- Conditions
- Dravet Syndrome
- Registration Number
- NCT04537832
- Lead Sponsor
- Encoded Therapeutics
- Brief Summary
This is a multicenter, prospective, 2-year observational study in infants and children with developmental and epileptic encephalopathies (DEEs). The DEE currently being investigated is SCN1A-positive Dravet Syndrome.
- Detailed Description
This prospective, longitudinal, natural history master protocol has been designed to define the seizure, neurodevelopmental, and behavioral characteristics of SCN1A-positive Dravet Syndrome in infants and children between 6 and 60 months. It will also explore the impact of the disease on the participant's parent/caregiver quality of life (QoL) and healthcare resource utilization (HCRU).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 58
- Aged between 6 months and 60 months.
- Confirmed SCN1A mutation.
- Normal development prior to onset of first seizure as defined by the Centers for Disease -Control and Prevention (CDC 2019).
- Onset of seizures between age 3 and 15 months, inclusive.
- Copy number variant of SCN1A, including SCN1A microdeletion, if affecting other genes.
- SCN1A mutation present on both alleles.
- Known pathogenic or clinically suspected mutation in a seizure-associated gene besides SCN1A.
- Confirmed mutation in a gene besides SCN1A that is known to increase the severity of the seizure phenotype.
- Known gain-of-function genetic mutation, as defined by functional studies, including p.Thr226Met.
- History of notable developmental deficit that was evident prior to seizure onset.
- Known central nervous system structural abnormality as found on magnetic resonance imaging or computed tomography scan of brain.
- Currently taking or has taken for 6 or more consecutive weeks anti-seizure medications (ASMs) at a therapeutic dose that are contraindicated in SCN1A-positive Dravet Syndrome, including sodium channel blockers.
- Known concomitant genetic mutation or clinical comorbidity that potentially confounds typical Dravet phenotype.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Seizure burden Change from Baseline at 24 months Measured using monthly seizure frequency derived from seizure diaries.
Use of Special Diet Change from Baseline at 24 months Measured using the incidence of ketogenic/high-fat diet usage observed during the 60 days leading up to each nominal visit.
Use of anti-seizure medication(s) Baseline through Month 24 Measured using the incidence of anti-seizure medication usage observed during the 60 days leading up to each nominal visit.
Behavioral and social functioning Change from Baseline at 24 months Measured using raw scores from 2 domains in the Brief Infant Toddler Social Emotional Assessment. Domains include: (1) Problem; and (2) Competence.
Domain raw scores range from 31 to 93 and 11 to 33 for the Problem and Competence domains, respectively. Higher Problem scores correspond to worse outcomes. Higher Competence scores correspond to better outcomesMotor functioning Baseline through Month 24 Measured using categorical outcomes of 7 motor items adapted from the Bayley Scales of Infant and Toddler Development instrument and NorthStar Ambulatory Assessment. Motor milestones include: (1) Sit unassisted for 30 seconds; (2) Walk with assistance; (3) Stand alone; (4) Walk alone; (5) Walk upstairs; (6) Run with Coordination; and (7)Jump forward.
Overall survival Baseline through Month 24 Measured using the incidence of death observed by a given time point during the study.
Seizure freedom Change from Baseline at 24 months Measured using the proportion of seizure-free days observed.
Cognitive functioning Change from Baseline at 24 months Measured using composite scores from 3 domains in the Bayley Scales of Infant and Toddler Development (3rd Edition) instrument. Domains include: (1) Cognitive; (2) Language; (3) Motor.
Composite scores are normalized to a mean and SD of 100 and 15, respectively (range is not applicable as the scores are unbounded). Higher scores correspond to better outcomes compared to a normal population.Incidence of Adverse Events Baseline through Month 24 Measured using the incidence of adverse events and serious adverse events (broken down by preferred term) observed during the study.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (16)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Northeast Regional Epilepsy Group
🇺🇸Hackensack, New Jersey, United States
Abigail Wexner Research Institute at Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Scroll for more (6 remaining)Children's Hospital Los Angeles🇺🇸Los Angeles, California, United States