International CDKL5 Clinical Research Network
ICCRN
Multi-Site Validation of Biomarkers and Core Clinical Outcome Measures for Clinical Trials Readiness in CDKL5 Deficiency Disorder
2 other identifiers
observational
1,000
2 countries
9
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Feb 2021
Longer than P75 for all trials
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 15, 2021
CompletedFirst Submitted
Initial submission to the registry
July 28, 2022
CompletedFirst Posted
Study publicly available on registry
September 28, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 15, 2027
ExpectedDecember 6, 2023
December 1, 2023
5 years
July 28, 2022
December 5, 2023
Conditions
Outcome Measures
Primary Outcomes (9)
CDKL5 Deficiency Disorder (CDD) Clinical Severity Assessment - Clinician (CCSA-Clinician)
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.
5 years
CDKL5 Deficiency Disorder (CDD) Clinical Severity Assessment - Caregiver (CCSA-Caregiver)
Measured by caregiver/parent rating of patient on a scale of 0-100 with a higher score indicating higher severity.
5 years
CDKL5 Deficiency Disorder (CDD) Development Questionnaire - Caregiver (CDQ-Caregiver)
Measured by caregiver/parent rating of patient on a scale of 0-100 with a higher score indicating higher severity.
5 years
Communication and Symbolic Behavior Scales - Developmental Profile Infant Toddler Checklist (CSBS-DP ITC)
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.
5 years
Sleep Disorder Scale for Children (SDSC)
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.
5 years
Quality of Life Inventory - Disability (QI-Disability)
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.
5 years
CDKL5 Deficiency Disorder (CDD) Gross Motor (CDD-Motor)
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.
5 years
CDKL5 Deficiency Disorder (CDD) Fine Motor (CDD-Hand)
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.
5 years
Electroencephalogram/Evoked Potentials (EEG/EP) characteristics in CDKL5 Deficiency Disorder.
Measured by correlations of EEG/EP with other study scales.
5 years
Secondary Outcomes (3)
Frequency of different mutations in the CDKL5 Deficiency Disorder population
5 years
Frequency of medications and their indications in the CDKL5 Deficiency Disorder population
5 years
Social Determinants of Health (SDOH) in CDKL5 Deficiency Disorder population
5 years
Interventions
No intervention administered as part of this study; observational only.
Eligibility Criteria
Patients with CDKL5 Deficiency Disorder (CDD).
You may qualify if:
- All children diagnosed with CDD age 1-month to 100 years of age that are receiving care at one of the study institutions or are registered with the International CDKL5 Disorder Database will be considered for the study population.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
University of California Los Angeles/UCLA Mattel Children's Hospital
Los Angeles, California, 90095, United States
University of Colorado Denver/Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Harvard Medical School/Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Washington University in St. Louis/St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
NYU Langone Health
New York, New York, 10016, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Baylor College of Medicine/ Texas Children's Hospital
Houston, Texas, 77030, United States
Telethon Kids Institute/Perth Children's Hospital
Perth, Nedlands Western Australia, 6009, Australia
Related Publications (9)
Olson HE, Daniels CI, Haviland I, Swanson LC, Greene CA, Denny AMM, Demarest ST, Pestana-Knight E, Zhang X, Moosa AN, Fidell A, Weisenberg JL, Suter B, Fu C, Neul JL, Percy AK, Marsh ED, Benke TA, Poduri A. Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder. J Neurodev Disord. 2021 Sep 16;13(1):40. doi: 10.1186/s11689-021-09384-z.
PMID: 34530725BACKGROUNDBrock D, Fidell A, Thomas J, Juarez-Colunga E, Benke TA, Demarest S. Cerebral Visual Impairment in CDKL5 Deficiency Disorder Correlates With Developmental Achievement. J Child Neurol. 2021 Oct;36(11):974-980. doi: 10.1177/08830738211019284.
PMID: 34547934BACKGROUNDSaldaris J, Weisenberg J, Pestana-Knight E, Marsh ED, Suter B, Rajaraman R, Heidary G, Olson HE, Devinsky O, Price D, Jacoby P, Leonard H, Benke TA, Demarest S, Downs J. Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder. J Child Neurol. 2021 Oct;36(11):998-1006. doi: 10.1177/08830738211019576. Epub 2021 Aug 11.
PMID: 34378447BACKGROUNDOlson HE, Costantini JG, Swanson LC, Kaufmann WE, Benke TA, Fulton AB, Hansen R, Poduri A, Heidary G. Cerebral visual impairment in CDKL5 deficiency disorder: vision as an outcome measure. Dev Med Child Neurol. 2021 Nov;63(11):1308-1315. doi: 10.1111/dmcn.14908. Epub 2021 May 24.
PMID: 34028805BACKGROUNDMacKay CI, Bick D, Prokop JW, Munoz I, Rouse J, Downs J, Leonard H. Expanding the phenotype of the CDKL5 deficiency disorder: Are seizures mandatory? Am J Med Genet A. 2020 May;182(5):1217-1222. doi: 10.1002/ajmg.a.61504. Epub 2020 Feb 8.
PMID: 32034940BACKGROUNDDale T, Downs J, Wong K, Leonard H. The perceived effects of cannabis products in the management of seizures in CDKL5 Deficiency Disorder. Epilepsy Behav. 2021 Sep;122:108152. doi: 10.1016/j.yebeh.2021.108152. Epub 2021 Jun 18.
PMID: 34148781BACKGROUNDLeonard H, Junaid M, Wong K, Demarest S, Downs J. Exploring quality of life in individuals with a severe developmental and epileptic encephalopathy, CDKL5 Deficiency Disorder. Epilepsy Res. 2021 Jan;169:106521. doi: 10.1016/j.eplepsyres.2020.106521. Epub 2020 Dec 1.
PMID: 33341033BACKGROUNDMacKay CI, Wong K, Demarest ST, Benke TA, Downs J, Leonard H. Exploring genotype-phenotype relationships in the CDKL5 deficiency disorder using an international dataset. Clin Genet. 2021 Jan;99(1):157-165. doi: 10.1111/cge.13862. Epub 2020 Oct 20.
PMID: 33047306BACKGROUNDBenke TA, Kind PC. Proof-of-concept for a gene replacement approach to CDKL5 deficiency disorder. Brain. 2020 Mar 1;143(3):716-718. doi: 10.1093/brain/awaa055.
PMID: 32203572BACKGROUND
MeSH Terms
Conditions
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy A Benke, MD PhD
University of Colorado, Denver
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 28, 2022
First Posted
September 28, 2022
Study Start
February 15, 2021
Primary Completion
February 15, 2026
Study Completion (Estimated)
February 15, 2027
Last Updated
December 6, 2023
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Available data will be released to the repository and will become available to the scientific community one year after publication of planned analyses, or after a period of 5 years from the date when the data were collected, whichever comes first.
- Access Criteria
- NIMH NDA policy will govern access criteria.
The ICCRN will be utilizing the National Institute of Mental Health (NIMH) Data Archive (NDA), previously known as the National Database for Autism Research (NDAR), as our final deidentified repository of our data. We will utilize Global Unique Identifiers to ensure we have deconflicted patient data across all institutions. Each institution will be directly uploading patient data to our central REDCap database to allow for cleaning of data prior to upload to NDA. Our data elements will be harmonized with other NDA elements where appropriate at the start of the study. The one exception is patient videos which will be reviewed at Telethon kids secure network for analysis, but the scored results of validated motor scales will be uploaded to NDAR in a deidentified fashion. All scales, outcome measures, and protocols (both for scoring and implementation of COMs) will also be shared through publications.