International CDKL5 Clinical Research Network

Condition(s) studied

Investigational drug(s) / intervention(s)

No intervention.: No intervention administered as part of this study; observational only.

Study summary

Pathogenic variants in the Cyclin-dependent kinase like 5 (CDKL5) gene cause CDKL5 deficiency disorder (CDD, MIM 300672, 105830), a severe developmental and epileptic encephalopathy associated with cognitive and motor impairments and cortical visual impairment. While capability for disease modifying therapies is accelerating, there is a critical barrier for clinical trial readiness that may result in failure of these therapies, not due to lack of efficacy but due to lack of validated outcome measures and biomarkers. The measures and biomarkers validated here will be adaptable to other developmental and epileptic encephalopathies.

Eligibility

Primary outcome measure(s)

• CDKL5 Deficiency Disorder (CDD) Clinical Severity Assessment - Clinician (CCSA-Clinician) — 5 years
  Measured by clinician rating of patient. Item scores are transformed to a scale of 0-100 and the total score is calculated as a mean item score. Higher scores indicate higher severity.
• CDKL5 Deficiency Disorder (CDD) Clinical Severity Assessment - Caregiver (CCSA-Caregiver) — 5 years
  Measured by caregiver/parent rating of patient on a scale of 0-100 with a higher score indicating higher severity.
• CDKL5 Deficiency Disorder (CDD) Development Questionnaire - Caregiver (CDQ-Caregiver) — 5 years
  Measured by caregiver/parent rating of patient on a scale of 0-100 with a higher score indicating higher severity.
• Communication and Symbolic Behavior Scales - Developmental Profile Infant Toddler Checklist (CSBS-DP ITC) — 5 years
  Measured by caregiver/parent rating of patient on a 24-item questionnaire. Three composite scores and a total score can be derived. Items contribute to the 0-57 point scale for the total score with lower scores indicating concerns for communication skills.
• Sleep Disorder Scale for Children (SDSC) — 5 years
  Measured by caregiver/parent rating of patient on a 26- Likert type item questionnaire. Scale goes from 0-39 with a higher score indicating higher severity of sleep disorder. Each subscale is scored through the summation of all the subscale items. Comparing scores were the normative data reported in the initial validation paper, z-scores and t-scores can be derived. The t-score enables scores to be dichotomized as within normal range or outside of normal range, compared to the general population.
• Quality of Life Inventory - Disability (QI-Disability) — 5 years
  This is a quality of life measure for children with intellectual disability. The measure comprises 32 items that are rated on a five-point Likert scale and group into six subscales: physical health, positive emotions, negative emotions, social interactions, independence, and leisure and outdoors. Following transformation to a 100-point scale, item scores in each subscale are summed and divided by the number of items to give a subscale score. The mean of the six subscale scores is calculated to give the total QOL score.
• CDKL5 Deficiency Disorder (CDD) Gross Motor (CDD-Motor) — 5 years
  This is a video measure of gross motor function, based on the Rett Syndrome Gross Motor Scale with additional items that enable measurement of head control and sitting. Parents are provided with a filming protocol, video clips are uploaded to the investigators, and data are coded according to a predetermined coding system.
• CDKL5 Deficiency Disorder (CDD) Fine Motor (CDD-Hand) — 5 years
  This is a video measure of fine motor function based on the Rett Syndrome Hand Function Scale with additional instructions on filming for if the patient has Cortical Visual Impairment. Parents are provided with a filming protocol, video clips are uploaded to the investigators, and data are coded according to a predetermined coding system.
• Electroencephalogram/Evoked Potentials (EEG/EP) characteristics in CDKL5 Deficiency Disorder. — 5 years
  Measured by correlations of EEG/EP with other study scales.

Trial sites (9)