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

NCT06448663 | Recruiting

• 1 other identifier: GSA23G001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

CDKL5

Keywords

epilepsy, gut microbiota, sleep disorders

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Gut microbiota

  Change at 3 months from baseline of each round of supplementation

• Sleep disturbances

  Change at 3 months from baseline of each round of supplementation

• gastrointestinal discomfort

  Change at 3 months from baseline of each round of supplementation

Other Outcomes (2)

• Clinical features

  Change at 3 months from baseline of each round of supplementation

• Parental stress

  Change at 3 months from baseline of each round of supplementation

Study Arms (1)

CDD arm

EXPERIMENTAL

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.

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

Interventions

alpha-lactalbumin, fructooligosaccharides, inulin DIETARY_SUPPLEMENT

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.

CDD arm

alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin DIETARY_SUPPLEMENT

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.

CDD arm

Eligibility Criteria

• Age: 3 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Milan: lead
• Fondazione Telethon: collaborator
• Kolfarma s.r.l. - Italy: collaborator

Study Sites (1)

University of Milan

Milan, Italy

RECRUITING

Related Publications (2)

• 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.

  PMID: 38548767 BACKGROUND

• Triva F, Borghi E, Marsiglia MD, Ottaviano E, Ricci E, Tognini P, Montecucco M, Vignoli A. 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 Oct 28;16:1642329. doi: 10.3389/fneur.2025.1642329. eCollection 2025.

  PMID: 41230376 DERIVED

MeSH Terms

Conditions

Epilepsy; Sleep Wake Disorders

Interventions

Lactalbumin; fructooligosaccharide; Inulin; Butyric Acid

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Intervention Hierarchy (Ancestors)

Albumins; Proteins; Amino Acids, Peptides, and Proteins; Whey Proteins; Milk Proteins; Animal Proteins, Dietary; Dietary Proteins; Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Aglaia Vignoli, MD

  University of Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aglaia Vignoli, MD

CONTACT

+390264443960; aglaia.vignoli@unimi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: April 1, 2024
• Primary Completion: January 31, 2025
• Study Completion: April 30, 2025
• Last Updated: June 7, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)