Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD) (NUTRIENT)

University of Milan

Status: Enrolling

Conditions: CDKL5

Treatments: Dietary Supplement: alpha-lactalbumin, fructooligosaccharides, inulin; Dietary Supplement: alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin

Study type: Interventional

Funder types: Other

Identifiers

NCT06448663

GSA23G001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 3 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

clinical diagnosis of CDD and demonstrated CDKL5 pathogenic variant; drug-resistant seizures; ensured participation of a caregiver; willingness to sign the informed consent.

Exclusion criteria

organic GI disorders (i.e., food allergies, celiac disease); special diets; percutaneous endoscopic gastrostomy tube; use of antibiotics or probiotics in the previous month.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

CDD arm

Experimental group

Description:

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.

Treatment:

Dietary Supplement: alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin

Dietary Supplement: alpha-lactalbumin, fructooligosaccharides, inulin