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

NCT ID: NCT06448663

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2025-04-30

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.

Conditions

CDKL5

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CDD arm

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.

Group Type: EXPERIMENTAL

alpha-lactalbumin, fructooligosaccharides, inulin

Intervention Type: 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.

alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin

Intervention Type: 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.

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Telethon

OTHER

Sponsor Role: collaborator

Kolfarma s.r.l. - Italy

UNKNOWN

Sponsor Role: collaborator

University of Milan

OTHER

Sponsor Role: lead

Responsible Party

Aglaia Vignoli

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Aglaia Vignoli, MD

Role: PRINCIPAL_INVESTIGATOR

University of Milan

Locations

University of Milan

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Aglaia Vignoli, MD

Role: CONTACT

aglaia.vignoli@unimi.it

+390264443960

Facility Contacts

Aglaia Vignoli, MD

Role: primary

aglaia.vignoli@unimi.it

+390264443960

References

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.

Reference Type: BACKGROUND

PMID: 38548767 (View on PubMed)

Other Identifiers

GSA23G001

Identifier Type: -

Identifier Source: org_study_id