Investigators are testing whether targeting the gut–brain axis can improve seizure control and neurological symptoms in CDKL5 deficiency disorder through a structured supplementation protocol.
Exploring the Gut–Brain Axis in CDD
Cyclin-dependent kinase-like 5 deficiency disorder is a severe neurodevelopmental condition marked by infantile-onset epilepsy that frequently remains resistant to standard anti-seizure medications. Persistent seizures can worsen developmental outcomes and diminish quality of life for affected children. Interest in the gut–brain axis has expanded across epilepsy research, particularly as gastrointestinal symptoms and altered gut microbiota have been noted in individuals with CDD. This emerging evidence has prompted researchers to examine whether a gut-targeted strategy could support seizure control and address broader neurological burdens.
Gut-Targeted Supplementation Strategy
The clinical protocol evaluates a sequential 24-week supplementation design intended to modulate the gut microbiota and reduce inflammation. During the first 12-week phase, participants receive alpha-lactalbumin, fructooligosaccharides, and inulin to support gut health and decrease inflammatory signaling. In the second phase, the same regimen is combined with sodium butyrate with the goal of promoting microbial balance and enhancing neuroprotective pathways. Throughout the trial, seizure frequency, sleep disturbances, and gastrointestinal discomfort are monitored to assess potential neurological and systemic effects. Stool samples are collected to analyze microbiota composition and evaluate how supplementation influences gut microbial structure.
Primary Objectives and Expected Impact
The primary aim is to determine whether modulating the gut–microbiota–brain axis through these targeted supplements can improve seizure control in children with CDKL5 deficiency disorder. A secondary objective is to explore links between microbial changes and clinical outcomes, supporting a deeper understanding of how gut-based interventions may influence disease presentation. Although results are pending, the trial represents an important step toward developing therapeutic options for drug-resistant epilepsy in this population and may inform future strategies for managing comorbid sleep and gastrointestinal disturbances.
Reference: Triva F et al. Targeting the gut to improve seizure control in CDKL5 deficiency disorder (CDD): study protocol for a single-arm, open-label clinical trial. Front Neurol. 2025;16:1642329.
