CNKSR2 Natural History Study
- Conditions
- Epileptic Encephalopathy, Childhood-OnsetX-Linked Intellectual DisabilityDevelopmental Dysphasia
- Registration Number
- NCT06500260
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
This prospective natural history study is being conducted to define the electroclinical, neurodevelopmental, and behavioral characteristics of CNKSR2 epilepsy aphasia syndrome (EAS) and intellectual disability (ID) in children aged 6 to 21 years old with CNKSR2 mutations.
The data collected from this study will serve as an external control to eventual clinical trials examining precision medicine investigational therapeutics that aim to improve the seizure burden and neurodevelopmental outcomes in patients with CNKSR2 EAS/ID.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
- Age between 6 and 21 years (inclusive) at time of consent.
- Confirmed CNKSR2 mutation, as demonstrated by genetic testing and confirmed by the investigators.
- Confirmed intellectual disability or developmental delays, as defined by the American Academy of Pediatrics (Moeschler, J, et al. 2014).
- Known pathogenic or clinically suspected mutation in a seizure-associated gene besides CNKSR2.
- Confirmed mutation in a gene besides CNKSR2 that is known to increase the severity of the seizure phenotype.
- Known central nervous system structural abnormality confirmed by imaging scan of the brain that is not consistent with the clinical phenotype of CNKSR2 EAS / ID.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change from baseline in resting state background brain activity during sleep as measured by phase lag index using electroencephalography (EEG). Baseline, Month 12, Month 24 Phase lag index ranges between 0 and 1 and is unitless. A phase lag index of zero indicates either no coupling or coupling with a phase difference centered around 0 mod π.
Change from baseline in functional connectivity within the language network using resting-state functional magnetic resonance imaging (fMRI). Baseline, Month 12, Month 24 Functional connectivity is unitless.
Change from baseline in neurodevelopmental status as measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) scaled scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Change from baseline in resting state brain activity as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG). Baseline, Month 12, Month 24 Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Change from baseline in neurodevelopmental status as measured by Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) scaled scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Change from baseline in functional connectivity within the epileptiform network using resting-state functional magnetic resonance imaging (fMRI). Baseline, Month 12, Month 24 Functional connectivity is unitless.
Change from baseline in cortical evoked response to self-produced speech as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG). Baseline, Month 12, Month 24 Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Change from baseline in neurodevelopmental status as measured by Parent Report Form of Vineland Adaptive Behavior Scales, 3rd Edition (Vineland-3) V-Scale Scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 1, maximum score: 24).
Change from baseline in performance on the Receptive One-Word Picture Vocabulary Test, 4th Edition standard scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: \< 55, maximum score: \> 165).
Change from baseline in ADHD Rating Scale, 4th Edition (ADHD-RS-IV) inattention subscale raw scores. Baseline, Month 6, Month 12, Month 18, Month 24 Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Change in physical functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores. Baseline, Month 6, Month 12, Month 18, Month 24 Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change in social functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores. Baseline, Month 6, Month 12, Month 18, Month 24 Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change from baseline in cortical evoked response to altered auditory feedback during self-produced speech as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG). Baseline, Month 12, Month 24 Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Change from baseline in spike-wave index during sleep as measured by percentage using electroencephalography (EEG). Baseline, Month 12, Month 24 Spike-wave index is the sum of all spike and slow wave minutes multiplied by 100 and divided by the total non-rapid eye movement sleep minutes.
Change from baseline in neurodevelopmental status as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) standard scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 45, maximum score: 155).
Change from baseline in neurodevelopmental status as measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) composite scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 40, maximum score: 160).
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) T-scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 20, maximum score: 80).
Change from baseline in performance on the Expressive One-Word Picture Vocabulary Test, 4th Edition standard scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: \< 55, maximum score: \> 165).
Change in emotional functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores. Baseline, Month 6, Month 12, Month 18, Month 24 Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) composite scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 40, maximum score: 160).
Change from baseline in neurodevelopmental status as measured by Parent Report Form of Vineland Adaptive Behavior Scales, 3rd Edition (Vineland-3) Adaptive Behavior Composite score and Domain scores. Baseline, Month 12, Month 24 Higher scores indicate a better outcome (minimum score: 20, maximum score: 140).
Change in hyperactivity as measured by ADHD Rating Scale, 4th Edition (ADHD-RS-IV) hyperactivity subscale raw scores. Baseline, Month 6, Month 12, Month 18, Month 24 Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Change in school functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores. Baseline, Month 6, Month 12, Month 18, Month 24 Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States