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

CDKL5 Clinical Trial

— NUTRIENT  

Official title:

Targeting the Gut to Improve Seizure Control in CDD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06448663
• Other study ID #: GSA23G001
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2024
• Source: University of Milan
• Contact: Aglaia Vignoli, MD
• Phone: +390264443960
• Email: aglaia.vignoli[@]unimi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 30, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• CDKL5
• Seizures

Intervention

Dietary Supplement:
• alpha-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.
• alpha-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.

Locations

Country	Name	City	State
Italy	University of Milan	Milan

Sponsors (3)

Lead Sponsor	Collaborator
University of Milan	Fondazione Telethon, Kolfarma s.r.l. - Italy

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Borghi E, Xynomilakis O, Ottaviano E, Ceccarani C, Vigano I, Tognini P, Vignoli A. Gut microbiota profile in CDKL5 deficiency disorder patients. Sci Rep. 2024 Mar 28;14(1):7376. doi: 10.1038/s41598-024-56989-0. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical features	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	Change at 3 months from baseline of each round of supplementation
Other	Parental stress	Caregiver burden by Parenting Stress Index (PSI-SF); clinically significance > 85%, decrease by at least 5%	Change at 3 months from baseline of each round of supplementation
Primary	Epilepsy	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	Change at 3 months from baseline of each round of supplementation
Secondary	Gut microbiota	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.	Change at 3 months from baseline of each round of supplementation
Secondary	Sleep disturbances	Decreased Sleep SDSC scale (max score=125) by at least 5%	Change at 3 months from baseline of each round of supplementation
Secondary	gastrointestinal discomfort	Decrease GISI scale (max score = 17), by at least 2 points	Change at 3 months from baseline of each round of supplementation