Summary

Eligibility
for people ages 1 month to 100 years (full criteria)
Location
at UCLA
Dates
study started
completion around
Principal Investigator
by Rajsekar Rajaraman, MD (ucla)

Description

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.

Official Title

Multi-Site Validation of Biomarkers and Core Clinical Outcome Measures for Clinical Trials Readiness in CDKL5 Deficiency Disorder

Details

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 (DEE) associated with cognitive and motor dysfunction and cortical visual impairment. Recent data suggest CDD is one of the most common genetic causes of DEE. Work in CDD animal models has demonstrated the ability for disease modification and symptom reversal: worldwide efforts are now underway to develop therapeutic strategies (including gene therapy) to treat and potentially cure CDD. While there are four active clinical trials, none assesses the full spectrum of this DEE to address true disease modification. 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.

CDD has been associated historically with Rett syndrome but there are many clear distinctions and CDD has emerged as an independent disorder. Some Clinical Outcome Measures (COMs) can be adapted from Rett syndrome COMs, whereas others need to be developed specifically for CDD. Our research network is uniquely positioned to develop clinical trial readiness for CDD by pairing exceptional experience in the development and validation of outcome measures with an extensive network of CDD experts and clinical trialists. Our goals are to 1) refine and validate appropriate quantitative COMs and biomarkers and 2) conduct a multi-site clinical trial readiness study to ensure that they can be successfully implemented. We will test the hypothesis that CDD specific COMs can be refined to accurately and reproducibly track meaningful changes in clinical trials:

Aim 1: Generate and validate a suite of COMs and biomarkers necessary to comprehensively assess disease modification in CDD.

Aim 2: Conduct a multi-site clinical trial readiness study to assess implementation, longitudinal stability, and collect baseline COMs and EEG/evoked potential data.

Overall Impact: These outcome measures will establish clinical trial readiness for CDD and generate historic baseline outcome data, ensuring optimal testing of potential new therapeutics including gene therapy. Furthermore, these measures will be adaptable to other DEEs by enabling choices of outcome measures beyond existing NINDS supported measurement tools (NeuroQoL, PROMIS, Toolbox) that are not designed for the severity of the DEE populations.

Keywords

CDKL5, CDKL5 Deficiency Disorder, CDD

Eligibility

You can join if…

Open to people ages 1 month to 100 years

  • 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.

You CAN'T join if...

- Individuals who do not meet study inclusion criteria.

Locations

  • University of California Los Angeles/UCLA Mattel Children's Hospital accepting new patients
    Los Angeles California 90095 United States
  • University of Colorado Denver/Children's Hospital Colorado accepting new patients
    Aurora Colorado 80045 United States

Lead Scientist at University of California Health

  • Rajsekar Rajaraman, MD (ucla)
    HS Assistant Clinical Professor, Pediatrics, Medicine. Authored (or co-authored) 20 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of Colorado, Denver
ID
NCT05558371
Study Type
Observational
Participants
Expecting 1000 study participants
Last Updated