Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness

OTHER

Observation

This intervention is observation only.

Change in Bayley Scales of Infant and Toddler Development (Fourth Edition)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

Bayley-4 is a standardized assessment tool designed to evaluate children from age 1 month to 42 months. Bayley-4 assesses multiple areas of development, including cognitive, language, motor, social/emotional, and adaptive behavior. It is considered a gold standard by clinicians and researchers. In clinical studies of developmental disorders, Bayley-4 can be used in children older than 42 months. We track scores using the "age equivalent" metric, which runs from 0 month to 42 months in each subdomain. We will explicitly track five domains: cognition, expressive language, receptive language, gross motor, and fine motor. This will result in 5 separate metrics for age equivalency.

Change in Observer-Reported Communication Ability (ORCA)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The ORCA is a battery of 84 questions to assess communication ability in children with neurodevelopmental disorders. Seventy items ask about observable behaviors within 22 concepts that cover expressive, receptive and pragmatic areas of communication. Fourteen additional items capture information about the individual's unique ways of communicating, including the modalities the individual uses, their current vocabulary, and aspects of language complexity (e.g. how many words/symbols/gestures are used to communicate a single message). The ORCA measure currently produces a single score that is an estimate of an individual's overall level of communication ability. Higher ORCA T-scores reflect greater communication ability; the mastery of expressive, receptive, and pragmatic types of communication and higher vocabularies for verbal words and symbols on assistive devices. The ORCA T-score range is from 25.8 to 83.8.

Change in Peabody Developmental Motor Scales 3 (PDMS-3)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

PDMS-3 is a standardized assessment tool used to measure the motor skills of young children from birth through 5 years of age. As with the Bayley-4, in studies of developmental disorders, the PDMS-3 is regularly used in children older than 5. We will track the age equivalent values in the five subdomains (body control, body transport, object control, hand manipulation, and eye-hand co-ordination). We track the "age equivalent" scores which range from 0 to 71 months in each subdomain. This will result in 5 "age equivalent" scores for each participant -- one for each subdomain.

Change in Pediatric Epilepsy Learning Healthcare System (PELHS)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

Dr. Grinspan (PI) designed the PELHS questions to characterize children with epilepsy for clinical care and research. These questions will be supplemented by standardized historical questions to understand the timing of critical events, such as the age of the first seizure, key EEG findings, and therapeutic trials. PELHS includes categorical items. Examples of categorical items include epilepsy syndrome and epilepsy type.

Change in QI-Disability

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

QI-Disability is a quality-of-life instrument specifically designed for children with intellectual disabilities with a strong track record of use in developmental and epileptic encephalopathies like CDKL5 disorder. Some core domains include physical, psychological, social, functional well-being, and self-determination. Each item is rated on a 5-point Likert scale and item scores are scaled to range from 0 to 100 with higher scores indicating better quality of life.

Change in Children's Sleep Habits Questionnaire (CSHQ)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

CHSQ is a parent survey focusing on bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night awakenings, and parasomnias. The scores range from 33 (no sleep disturbances) to 99 (profound sleep disturbances). Scores of 41 or higher indicate clinically significant sleep disturbance. We will analyze this variable as a binary variable (\< 41 vs \>= 41).

Change in Childhood Autism Rating Scale-2 (CARS-2)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The CARS-2 is a diagnostic tool used to assess the severity of the autism spectrum disorder in children as young as 2. It consists of 15 items, each of which is rated on a scale from 1-4 (i.e. total score ranges from 15 to 60). Scores from 15-29.5 reflect minimal-to-no symptoms of autism spectrum disorder, scores from 30-36.5 reflect mild-to-moderate symptoms of autism spectrum disorder, and scores from 37-60 reflect severe symptoms of autism spectrum disorder. We will analyze these data as an ordinal categorical variable (four levels).

Change in Vineland Adaptive Behavior Scales (Third Edition)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The Vineland Scales are a standard assessment of development for all ages. We will focus on five domains. For the adaptive behavior score, we will use the standard score -- the range is from 20 (lowest) to 140 (highest). For gross motor and fine motor domains, we will track the age equivalent value (range from 0 months to 83 months). For receptive and expressive language, we will also track the age equivalent value (range from 0 months to 252 months). There will be a total of four age equivalent values per participant (one for each domain).

Change in Communication Function Classification System (CFCS)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

CFCS is a single-item, five-level scale to assess communication abilities, originally designed for people with cerebral palsy. It describes the ability of individuals to send and receive information with familiar and unfamiliar communication partners. A level 5 score represents least effective communication, while a level 1 score represents most effective communication.

Change in Alberta Infant Motor Scale (AIMS)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The AIMS is a standardized assessment tool used to evaluate the motor development of infants from birth to 18 months of age, focusing on gross motor skills, consisting of 58 items. The lowest possible score is 0 and the highest possible score is 58. We will provide interpretation by estimating the age-equivalent based on the 50%ile age associated with each score based on the normative percentile curves provided with the AIMS assessment worksheets -- for example a score of 3 is roughly equivalent to 0 months and a score of 50 is roughly equivalent to 11 months.

Change in Gross Motor Function Measure-88 (GMFM-88)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The GMFM-88 is a standardized clinical tool to evaluate changes in gross motor function in children aged 5 months and up. The scores range from 0-100, with a higher score indicating higher gross motor function.

Change in Gross Motor Function Classification System (GMFCS)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

GMFCS is a single-item, five-level scale to assess motor function, originally designed for people with cerebral palsy. It focuses on the degree of support required to maneuver in the environment. Scores range from I (least impaired) to V (most impaired).

Change in Manual Ability Classification System (MACS)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

MACS is a single-item, five-level scale to describe manual (hand and arm) abilities, initially designed for people with cerebral palsy. It measures how well children can handle objects, focusing on speed, accuracy, and requirements for support. The scores range from I (least impaired) to V (most impaired).

Change in WHO Motor Milestones

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The WHO Motor Development Milestones are part of a standardized framework developed through the WHO Multicenter Growth Reference Study. These milestones focus on six key gross motor skills: sitting without support, standing with assistance, hands-and-knees crawling, walking with assistance, standing alone, and walking alone. Rather than a numbered score, these motor milestones are given "windows of achievement" for the following ages: Sitting without support: 3.8 to 9.2 months Standing with assistance: 4.8 to 11.4 months Hands-and-knees crawling: 5.2 to 13.5 months Walking with assistance: 5.9 to 13.7 months Standing alone: 6.9 to 16.9 months Walking alone: 8.2 to 17.6 months

Change in Seizure Diaries

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The seizure diaries are caregiver-maintained records of a participant's seizure count and frequency. Each round of diary collection will provide a number of seizures per six weeks. We will track this quantitatively as "seizures per week".

Change in Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

PELHS-QOL-2 is a brief, validated, 2-question assessment of quality of life for children with epilepsy. It can be scored from 0 (no impact of seizures or medication side effects on usual routines) to 8 (daily impact of seizures and side effects on usual routines).

Change in Pediatric Sleep Questionnaire (PSQ)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The PSQ evaluates sleep-related breathing disorders, snoring, and daytime sleepiness in children. The PSQ has a score range from 0 to 1, with a higher score indicating a higher likelihood for sleep-related breathing disorders.

Change in Aberrant Behavior Checklist (ABC)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The ABC is a validated scale to measure psychiatric symptoms and behavioral disturbance in children with intellectual disabilities. The lowest possible score of 0 indicates no aberrant behaviors. The highest possible score is 174. Higher scores indicate a higher degree of aberrant behavior.

Change in Seizure Diaries

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The seizure diaries are caregiver-maintained records of a participant's seizure count and frequency. Each round of diary collection will provide a number of seizures per six weeks. We will track the percentage of participants who have 50% reduction in seizure frequency at each visit compared to the prior visit.

Change in Mullen Scales of Early Learning

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

Information about cognitive functioning is generated in four distinct areas (visual reception, fine motor, receptive language, and expressive language scales). There also is a measure of gross motor skills.The Mullen Scales provides a composite score. The lowest possible raw score in each subsection is a 5, for a lowest possible overall score of 25. The highest possible composite score is 218.

Change in (DAYC-2) Developmental Assessment of Young Children, Second Edition

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The DAYC-2 is a popular test used to identify children birth through 5-11 with possible delays in the following domains: cognition, communication, social-emotional development, physical development, and adaptive behavior. The domains can be assessed independently, so examiners may test only the domains that interest them or test all five domains when a measure of general development is desired. The lowest possible raw score is 0, while the highest possible raw score is 253.

Change in Children's Sleep Habits Questionnaire (CSHQ)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

CHSQ is a parent survey focusing on bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night awakenings, and parasomnias. The scores range from 33 (no sleep disturbances) to 99 (profound sleep disturbances). Scores of 41 or higher indicate clinically significant sleep disturbance. We will analyze this variable as a continuous variable (33 to 99).

Change in Childhood Autism Rating Scale-2 (CARS-2)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The CARS-2 is a diagnostic tool used to assess the severity of the autism spectrum disorder in children as young as 2. It consists of 15 items, each of which is rated on a scale from 1-4 (i.e. total score ranges from 15 to 60). Scores from 15-29.5 reflect minimal-to-no symptoms of autism spectrum disorder, scores from 30-36.5 reflect mild-to-moderate symptoms of autism spectrum disorder, and scores from 37-60 reflect severe symptoms of autism spectrum disorder. We will analyze these data as a continuous variable (score value).

Change in Pediatric Epilepsy Learning Healthcare System (PELHS)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

Dr. Grinspan (PI) designed the PELHS questions to characterize children with epilepsy for clinical care and research. These questions will be supplemented by standardized historical questions to understand the timing of critical events, such as the age of the first seizure, key EEG findings, and therapeutic trials. PELHS includes ordinal items. Examples of ordinal items include seizure frequency (range from "none in the past two years" to "too many to count") and age of epilepsy onset. There is no overall score.

Change in Aberrant Behavior Checklist (ABC)

Time frame: at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

The ABC is a validated scale to measure psychiatric symptoms and behavioral disturbance in children with intellectual disabilities. We will track each of five subdomains -- irritability (score range 0 - 45), lethargy (0 - 48), stereotypy (0 - 21), hyperactivity (0 - 48), inappropriate speech (0 -12).

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.