Developmental DysphasiaCNKSR2NCT06500260
CNKSR2 Natural History Study
An observational study of Developmental Dysphasia and Epileptic Encephalopathy, Childhood-Onset, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 21 years
- Conditions the study is for
- Developmental Dysphasia, Epileptic Encephalopathy, Childhood-Onset, X-Linked Intellectual Disability
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2022to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children with CNKSR2 pathogenic mutation and characteristic features of CNKSR2 neurodevelopmental disorder and/or epilepsy
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco (UCSF)
San Francisco, California, 94158
About this study
Official title: Natural History Study of Infants and Children With CNKSR2-Associated Neurodevelopmental Disorders and Epilepsy
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.
- Conditions
- Developmental Dysphasia, Epileptic Encephalopathy, Childhood-Onset, X-Linked Intellectual Disability
- Keywords
- X-linked Intellectual Disability, ESES, CSWS, CNKSR2, Epilepsy, Language Disorder
- Medical subject headings
- X-Linked Intellectual Disability, Epilepsy, Language Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in functional connectivity within the epileptiform network using resting-state functional magnetic resonance imaging (fMRI).
Functional connectivity is unitless.
Measured: Baseline, Month 12, Month 24
Change from baseline in functional connectivity within the language network using resting-state functional magnetic resonance imaging (fMRI).
Functional connectivity is unitless.
Measured: Baseline, Month 12, Month 24
Change from baseline in cortical evoked response to self-produced speech as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Measured: Baseline, Month 12, Month 24
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).
Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Measured: Baseline, Month 12, Month 24
Change from baseline in resting state brain activity as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Measured: Baseline, Month 12, Month 24
Change from baseline in resting state background brain activity during sleep as measured by phase lag index using electroencephalography (EEG).
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.
Measured: Baseline, Month 12, Month 24
Change from baseline in spike-wave index during sleep as measured by percentage using electroencephalography (EEG).
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.
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) scaled scores.
Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) standard scores.
Higher scores indicate a better outcome (minimum score: 45, maximum score: 155).
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) composite scores.
Higher scores indicate a better outcome (minimum score: 40, maximum score: 160).
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) scaled scores.
Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) composite scores.
Higher scores indicate a better outcome (minimum score: 40, maximum score: 160).
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) T-scores.
Higher scores indicate a better outcome (minimum score: 20, maximum score: 80).
Measured: Baseline, Month 12, Month 24
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.
Higher scores indicate a better outcome (minimum score: 20, maximum score: 140).
Measured: Baseline, Month 12, Month 24
Change from baseline in neurodevelopmental status as measured by Parent Report Form of Vineland Adaptive Behavior Scales, 3rd Edition (Vineland-3) V-Scale Scores.
Higher scores indicate a better outcome (minimum score: 1, maximum score: 24).
Measured: Baseline, Month 12, Month 24
Change from baseline in performance on the Receptive One-Word Picture Vocabulary Test, 4th Edition standard scores.
Higher scores indicate a better outcome (minimum score: < 55, maximum score: > 165).
Measured: Baseline, Month 12, Month 24
Change from baseline in performance on the Expressive One-Word Picture Vocabulary Test, 4th Edition standard scores.
Higher scores indicate a better outcome (minimum score: < 55, maximum score: > 165).
Measured: Baseline, Month 12, Month 24
Change from baseline in ADHD Rating Scale, 4th Edition (ADHD-RS-IV) inattention subscale raw scores.
Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Measured: Baseline, Month 6, Month 12, Month 18, Month 24
Change in hyperactivity as measured by ADHD Rating Scale, 4th Edition (ADHD-RS-IV) hyperactivity subscale raw scores.
Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Measured: Baseline, Month 6, Month 12, Month 18, Month 24
Change in physical functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Measured: Baseline, Month 6, Month 12, Month 18, Month 24
Change in emotional functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Measured: Baseline, Month 6, Month 12, Month 18, Month 24
Change in social functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Measured: Baseline, Month 6, Month 12, Month 18, Month 24
Change in school functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Measured: Baseline, Month 6, Month 12, Month 18, Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2024
- Study start1 Jan 2022
- Primary completion30 Apr 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Developmental DysphasiaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alex Fay, MD, PhD, Principal investigator, alexander.fay@ucsf.edu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06500260
- Sponsor's protocol ID
- 22-35959
- Acronym
- CNKSR2
- Status last verified
- Jul 2026
- First submitted
- 1 Mar 2024
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Infants and Children With CNKSR2-Associated Neurodevelopmental Disorders and Epilepsy
- ClinicalTrials.gov ID
- NCT06500260
- Acronym / sponsor ID
- CNKSR2 / 22-35959
- Conditions
- Developmental Dysphasia, Epileptic Encephalopathy, Childhood-Onset, X-Linked Intellectual Disability
- Keywords
- X-linked Intellectual Disability, ESES, CSWS, CNKSR2, Epilepsy, Language Disorder
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 15 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children with CNKSR2 pathogenic mutation and characteristic features of CNKSR2 neurodevelopmental disorder and/or epilepsy
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change from baseline in functional connectivity within the epileptiform network using resting-state functional magnetic resonance imaging (fMRI).
Time frame: Baseline, Month 12, Month 24
Functional connectivity is unitless.
Change from baseline in functional connectivity within the language network using resting-state functional magnetic resonance imaging (fMRI).
Time frame: 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).
Time frame: 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 cortical evoked response to altered auditory feedback during self-produced speech as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Time frame: 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 resting state brain activity as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Time frame: 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 resting state background brain activity during sleep as measured by phase lag index using electroencephalography (EEG).
Time frame: 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 spike-wave index during sleep as measured by percentage using electroencephalography (EEG).
Time frame: 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 Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) scaled scores.
Time frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Change from baseline in neurodevelopmental status as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) standard scores.
Time frame: 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.
Time frame: 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 Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) scaled scores.
Time frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) composite scores.
Time frame: 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.
Time frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 20, maximum score: 80).
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.
Time frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 20, maximum score: 140).
Change from baseline in neurodevelopmental status as measured by Parent Report Form of Vineland Adaptive Behavior Scales, 3rd Edition (Vineland-3) V-Scale Scores.
Time frame: 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.
Time frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: < 55, maximum score: > 165).
Change from baseline in performance on the Expressive One-Word Picture Vocabulary Test, 4th Edition standard scores.
Time frame: 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.
Time frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Change in hyperactivity as measured by ADHD Rating Scale, 4th Edition (ADHD-RS-IV) hyperactivity subscale raw scores.
Time frame: 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.
Time frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change in emotional functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Time frame: 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.
Time frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change in school functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Time frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alex Fay, MD, PhD principal investigator
alexander.fay@ucsf.edu
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Developmental Dysphasia and Epileptic Encephalopathy, Childhood-Onset, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in functional connectivity within the epileptiform network using resting-state functional magnetic resonance imaging (fMRI). (time frame: Baseline, Month 12, Month 24). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.