Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD)
- Conditions
- CDKL5
- Interventions
- Dietary Supplement: alpha-lactalbumin, fructooligosaccharides, inulinDietary Supplement: alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin
- Registration Number
- NCT06448663
- Lead Sponsor
- University of Milan
- Brief Summary
Standard anti-seizure medications have limited efficacy in seizure control in cyclin-dependent kinase-like 5 deficiency disorder (CDD).
The study will investigate whether targeting the gut-microbiota-brain axis in CDD patients can alleviate seizures and ameliorate other comorbidities.
- Detailed Description
CDD is a neurodevelopmental condition characterized by infantile-onset epilepsy, developmental delays, intellectual and motor disabilities, sleep disturbances, and cortical visual impairment. Currently, there is no treatment for CDD, and epilepsy is a prominent and severe feature of the disorder. Standard anti-seizure medications have limited efficacy in seizure control, leading to detrimental effects on cognitive and motor development in CDD.
The gut-brain axis has gained attention in epilepsy research, prompted by evidence of gastrointestinal (GI) symptoms in people with epilepsy. Studies have demonstrated significant changes in gut microbial composition in animal models and between individuals with epilepsy and healthy subjects. Notably, CDD patients experience GI problems, and we discovered that they exhibit alterations in their gut microbiota compared to healthy individuals. The study will investigate whether supplementing CDD patients with alpha-lactalbum and prebiotics alone or with post-biotics can improve neurological features and modulate microbiota composition.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
clinical diagnosis of CDD and demonstrated CDKL5 pathogenic variant; drug-resistant seizures; ensured participation of a caregiver; willingness to sign the informed consent.
organic GI disorders (i.e., food allergies, celiac disease); special diets; percutaneous endoscopic gastrostomy tube; use of antibiotics or probiotics in the previous month.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CDD arm alpha-lactalbumin, fructooligosaccharides, inulin This is a 32-week pilot, single site, cross-over trial of alpha-lactalbumin+ inulin + fructo-oligosaccharides vs alpha-lactalbumin + sodium butyrate + inulin + fructo-oligosaccharides. Periods I and II of the study are 12-week long together with a 4-week washout period. CDD arm alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin This is a 32-week pilot, single site, cross-over trial of alpha-lactalbumin+ inulin + fructo-oligosaccharides vs alpha-lactalbumin + sodium butyrate + inulin + fructo-oligosaccharides. Periods I and II of the study are 12-week long together with a 4-week washout period.
- Primary Outcome Measures
Name Time Method Epilepsy Change at 3 months from baseline of each round of supplementation to evaluate the number of CDD patients considered treatment responders (seizure reduction ≥50%, ≥75% or ≥100% from baseline in monthly seizure counts) during the 12- week treatment period in 1st and 2nd round of supplementation
- Secondary Outcome Measures
Name Time Method Gut microbiota Change at 3 months from baseline of each round of supplementation to evaluate indicator species that could help as biomarkers for guiding clinicians to choose the intervention with the most likelihood of improve patient quality of life.
Sleep disturbances Change at 3 months from baseline of each round of supplementation Decreased Sleep SDSC scale (max score=125) by at least 5%
gastrointestinal discomfort Change at 3 months from baseline of each round of supplementation Decrease GISI scale (max score = 17), by at least 2 points
Trial Locations
- Locations (1)
University of Milan
🇮🇹Milan, Italy