The goal of this observational study is to learn about the impact of the diabetes drug glibenclamide (glyburide) on neurodevelopment in individuals with iDEND (developmental delay, epilepsy and neonatal diabetes) due to the V59M mutation in the KCNJ11 gene. The main question it aims to answer is whether initiating sulphonylurea (SU) therapy in the first year of life results in better neurodevelopmental outcomes in affected individuals, in comparison to starting therapy later than 12 months of age.
Participants will undergo a neurodevelopmental assessment comprising parental and teacher completion of standardised questionnaires, and where possible face to face neuropsychological testing.
Researchers will compare the outcomes of these standardised tests in the individuals who started SU therapy \<12 months of age in comparison to those who started \>12 months of age.
Current age ≥2 years
Heterozygous for a V59M mutation in the KCNJ11 gene
Successfully transferred to oral sulphonylurea therapy
Willing to participate
Never able to transfer to oral sulphonylurea therapy
Unwilling to participate
Participating centres will recruit and assess participants meeting study eligibility criteria (University of Exeter, UK, University of Chicago, USA, University of Bergen, Norway and University of Rome, Italy). Participants will be allocated to the early treatment or late treatment group depending on age at initiation of SU therapy, in a ratio of 1:2 (early:late).
Case-control
Retrospective
Sulfonylurea
DrugGlibenlclamide / glyburide
Number and type of neurodevelopmental and psychiatric disorders
Measured by Development and Wellbeing Assessment (DAWBA)
Level of difficulty due to neurodevelopmental and psychiatric morbidity
Measured by Strengths and Difficulties Questionnaire (SDQ) total difficulties score. Scores range from 0-40 with higher scores indicating greater difficulties. Scores will be converted to Z-scores using normative population data for the purposes of analysis.
Impact on daily life
Measured by SDQ impact score. Scores range from 0-10 for parent and self-report and 0-6 for teacher report, with higher scores indicating greater difficulties. Scores will be converted to Z-scores using normative population data for the purposes of analysis.
IQ score
Measured by Leiter-3 International Performance Scale
Major milestones
Measured by parent report / review of clinical records
Communication difficulties
Measured by the Children's Communication Checklist 2 (CCC-2) questionnaire, consisting of 70 items scored by parents / caregivers. Lower scores indicate more communication difficulties.
Hyperactivity, emotional problems, conduct problems, peer relationships, prosocial behaviour.
Measured by SDQ subsections. Scores range from 0-10 for each subsection with higher scores indicating greater difficulties, except prosocial score where lower scores indicate greater difficulties. Scores will be converted to Z-scores using normative population data for the purposes of analysis.
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Royal Devon and Exeter NHS Foundation Trust
Lead sponsor
University of Chicago
Collaborator
University of Bergen
Collaborator
University of Rome Tor Vergata
Collaborator
