CDKL5
Conditions
Keywords
epilepsy, gut microbiota, sleep disorders
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.
Interventions
DIETARY_SUPPLEMENTalpha-lactalbumin, fructooligosaccharides, inulin
The first round supplementation will be administered for 3-month period (i.e. 12 weeks). One dose/day (2g sachet) is intended to be administered orally once a day after dissolving in water. At the scheduled visits/phone contacts \[i.e., baseline, 12 weeks, and 16 weeks (post washout)\], seizure frequency and entity of the critical episodes will be recorded. Gut microbiome characterization, clinical scales and dietary intake will be assessed.
DIETARY_SUPPLEMENTalpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin
The second round supplementation will be administered for 3-month period (i.e. 12 weeks). For participants weighing \<30 kg, a 4 g dose (i.e., one 4 g sachet) is intended to be administered orally once a day after dissolving in water. For participants weighing ≥30 kg, a 4 g dose (i.e., 4 g sachets) is intended to be administered orally twice a day (12h interval) after dissolving in water. At the scheduled visits/phone contacts \[i.e., 28 weeks and 32 weeks (post washout)\], seizure frequency and entity of the critical episodes will be recorded. Gut microbiome characterization, clinical scales and dietary intake will be assessed.
Sponsors
Fondazione Telethon
Kolfarma s.r.l. - Italy
University of Milan
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinical features | Change at 3 months from baseline of each round of supplementation | Clinical Global Impression of Change (CGIC), ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change\] decrease of at least 1 point |
| Parental stress | Change at 3 months from baseline of each round of supplementation | Caregiver burden by Parenting Stress Index (PSI-SF); clinically significance \> 85%, decrease by at least 5% |
Countries
Italy
Contacts
Primary ContactAglaia Vignoli, MD
Outcome results
None listed