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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05558371
Registration number
NCT05558371
Ethics application status
Date submitted
28/07/2022
Date registered
28/09/2022
Titles & IDs
Public title
International CDKL5 Clinical Research Network
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Scientific title
Multi-Site Validation of Biomarkers and Core Clinical Outcome Measures for Clinical Trials Readiness in CDKL5 Deficiency Disorder
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Secondary ID [1]
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5U01NS114312
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Secondary ID [2]
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19-2756
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Universal Trial Number (UTN)
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Trial acronym
ICCRN
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
CDKL5
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CDKL5 Deficiency Disorder
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CDD
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Condition category
Condition code
Intervention/exposure
Study type
Observational
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Patient registry
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Target follow-up duration
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Target follow-up type
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Description of intervention(s) / exposure
Other interventions - No intervention.
Other interventions: No intervention.
No intervention administered as part of this study; observational only.
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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CDKL5 Deficiency Disorder (CDD) Clinical Severity Assessment - Clinician (CCSA-Clinician)
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Assessment method [1]
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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.
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Timepoint [1]
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5 years
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Primary outcome [2]
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CDKL5 Deficiency Disorder (CDD) Clinical Severity Assessment - Caregiver (CCSA-Caregiver)
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Assessment method [2]
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Measured by caregiver/parent rating of patient on a scale of 0-100 with a higher score indicating higher severity.
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Timepoint [2]
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5 years
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Primary outcome [3]
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CDKL5 Deficiency Disorder (CDD) Development Questionnaire - Caregiver (CDQ-Caregiver)
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Assessment method [3]
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Measured by caregiver/parent rating of patient on a scale of 0-100 with a higher score indicating higher severity.
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Timepoint [3]
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5 years
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Primary outcome [4]
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Communication and Symbolic Behavior Scales - Developmental Profile Infant Toddler Checklist (CSBS-DP ITC)
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Assessment method [4]
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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.
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Timepoint [4]
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5 years
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Primary outcome [5]
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Sleep Disorder Scale for Children (SDSC)
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Assessment method [5]
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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.
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Timepoint [5]
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5 years
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Primary outcome [6]
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Quality of Life Inventory - Disability (QI-Disability)
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Assessment method [6]
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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.
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Timepoint [6]
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5 years
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Primary outcome [7]
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CDKL5 Deficiency Disorder (CDD) Gross Motor (CDD-Motor)
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Assessment method [7]
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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.
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Timepoint [7]
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5 years
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Primary outcome [8]
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CDKL5 Deficiency Disorder (CDD) Fine Motor (CDD-Hand)
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Assessment method [8]
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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.
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Timepoint [8]
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5 years
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Primary outcome [9]
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Electroencephalogram/Evoked Potentials (EEG/EP) characteristics in CDKL5 Deficiency Disorder.
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Assessment method [9]
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Measured by correlations of EEG/EP with other study scales.
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Timepoint [9]
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5 years
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Secondary outcome [1]
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Frequency of different mutations in the CDKL5 Deficiency Disorder population
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Assessment method [1]
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Measured by information obtained from genetic reports of enrolled participants.
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Timepoint [1]
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5 years
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Secondary outcome [2]
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Frequency of medications and their indications in the CDKL5 Deficiency Disorder population
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Assessment method [2]
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Measured by medication/indication data obtained from medical record review and/or caregiver report.
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Timepoint [2]
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5 years
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Secondary outcome [3]
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Social Determinants of Health (SDOH) in CDKL5 Deficiency Disorder population
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Assessment method [3]
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Measured by data elements that are collected to describe the socioeconomic status of the study population. Examples include caregiver education level, marital status and employment status, patient living situation, household income, and primary caregiver information.
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Timepoint [3]
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5 years
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Eligibility
Key inclusion criteria
* 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.
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Minimum age
1
Month
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Maximum age
100
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Individuals who do not meet study inclusion criteria.
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Study design
Purpose
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Duration
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Selection
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Timing
Prospective
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
15/02/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
15/02/2027
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Actual
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Sample size
Target
1000
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
Nedlands WA
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Recruitment hospital [1]
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Telethon Kids Institute/Perth Children's Hospital - Perth
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Recruitment postcode(s) [1]
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6009 - Perth
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Colorado
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Country [3]
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United States of America
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State/province [3]
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Massachusetts
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Country [4]
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United States of America
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State/province [4]
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Missouri
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Country [5]
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United States of America
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State/province [5]
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New York
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Country [6]
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United States of America
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State/province [6]
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Ohio
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Country [7]
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United States of America
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State/province [7]
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Pennsylvania
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Country [8]
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United States of America
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State/province [8]
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Texas
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Funding & Sponsors
Primary sponsor type
Other
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Name
University of Colorado, Denver
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Address
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Country
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Other collaborator category [1]
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Government body
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Name [1]
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National Institute of Neurological Disorders and Stroke (NINDS)
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Address [1]
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Country [1]
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Other collaborator category [2]
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Government body
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Name [2]
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National Institutes of Health (NIH)
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Address [2]
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Country [2]
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Other collaborator category [3]
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Other
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Name [3]
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International Foundation for CDKL5 Research
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Address [3]
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Country [3]
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT05558371
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Trial related presentations / publications
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. Brock 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. Saldaris 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. Olson 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. MacKay 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. Dale 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. Leonard 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. MacKay 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. Benke 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.
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Public notes
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Contacts
Principal investigator
Name
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Timothy A Benke, MD PhD
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Address
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University of Colorado, Denver
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Sharon R Pincus, MA
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Address
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Phone
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303-949-7116
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
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.
Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
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When will data be available (start and end dates)?
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.
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Available to whom?
NIMH NDA policy will govern access criteria.
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://nda.nih.gov/
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05558371