CDKL5NUTRIENTNCT06448663
Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD)
A study testing alpha-lactalbumin, fructooligosaccharides, inulin and alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin in people with CDKL5, run by University of Milan at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 3 to 50 years
- Conditions the study is for
- CDKL5
- What is being tested?
- alpha-lactalbumin, fructooligosaccharides, inulin and alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 1 Apr 2024to 30 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- clinical diagnosis of CDD and demonstrated CDKL5 pathogenic variant; drug-resistant seizures; ensured participation of a caregiver; willingness to sign the informed consent.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University of Milan
Milan
Aglaia Vignoli, MD, +390264443960, aglaia.vignoli@unimi.it
Elisa Borghi, PhD
About this study
Official title: Targeting the Gut to Improve Seizure Control in CDD
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.
Read the 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
- Being tested
- alpha-lactalbumin, fructooligosaccharides, inulin, alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin
- Keywords
- epilepsy, gut microbiota, sleep disorders
- Medical subject headings
- Epilepsy, Sleep Wake Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alpha-lactalbumin, fructooligosaccharides, inulinDietary 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, inulinDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: alpha-lactalbumin, fructooligosaccharides, inulin; Dietary Supplement: alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Change at 3 months from baseline of each round of supplementation
Secondary outcomes (3)
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.
Measured: Change at 3 months from baseline of each round of supplementation
Sleep disturbances
Decreased Sleep SDSC scale (max score=125) by at least 5%
Measured: Change at 3 months from baseline of each round of supplementation
gastrointestinal discomfort
Decrease GISI scale (max score = 17), by at least 2 points
Measured: Change at 3 months from baseline of each round of supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2024
- Study start1 Apr 2024
- Primary completion31 Jan 2025 (estimated)
- Study completion30 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CDKL5Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione Telethon, Kolfarma s.r.l. - Italy
- Responsible party
- Principal investigator, Aglaia Vignoli, University of Milan
- Investigators
- Aglaia Vignoli, MD, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06448663
- Sponsor's protocol ID
- GSA23G001
- Acronym
- NUTRIENT
- Status last verified
- Jun 2024
- First submitted
- 3 Jun 2024
- Last updated
- 7 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38548767Triva 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.
PubMed 41230376
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting the Gut to Improve Seizure Control in CDD
- ClinicalTrials.gov ID
- NCT06448663
- Acronym / sponsor ID
- NUTRIENT / GSA23G001
- Conditions
- CDKL5
- Keywords
- epilepsy, gut microbiota, sleep disorders
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Collaborators
- Fondazione Telethon, Kolfarma s.r.l. - Italy
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 7 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CDD arm | Experimental | Dietary Supplement: alpha-lactalbumin, fructooligosaccharides, inulin, Dietary Supplement: alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulinThis 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. |
Who may qualify
- Ages
- 3 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- clinical diagnosis of CDD and demonstrated CDKL5 pathogenic variant; drug-resistant seizures; ensured participation of a caregiver; willingness to sign the informed consent.
Key exclusion criteria (1 listed)
- organic GI disorders (i.e., food allergies, celiac disease); special diets; percutaneous endoscopic gastrostomy tube; use of antibiotics or probiotics in the previous month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| alpha-lactalbumin, fructooligosaccharides, inulinThe 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 supplement | CDD arm |
| alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulinThe 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. | Dietary supplement | CDD arm |
Primary outcome
Epilepsy
Time frame: 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
3 secondary outcomes
Gut microbiota
Time frame: Change at 3 months from baseline of each round of supplementation
Sleep disturbances
Time frame: Change at 3 months from baseline of each round of supplementation
gastrointestinal discomfort
Time frame: Change at 3 months from baseline of each round of supplementation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
- Background: PubMed 38548767Borghi 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.
- Derived from this study: PubMed 41230376Triva 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aglaia Vignoli, MD principal investigator
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing alpha-lactalbumin, fructooligosaccharides, inulin and alpha-lactalbumin, sodium butyrate, fructooligosaccharides, inulin in people with CDKL5, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aglaia Vignoli, MD (+390264443960, aglaia.vignoli@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epilepsy (time frame: Change at 3 months from baseline of each round of supplementation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06448663, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2024.