EpilepsyNCT05898438
The Role of Gut Microbiota in Children With Epilepsy Following Ketogenic Diet
An observational study of Epilepsy, run by Attikon Hospital at 1 site in Greece.
Trial summary
The role of human microbiota in neurological disorders via the "microbiota-gut-brain axis" is recently gaining increased attention due to the knowledge that gut microorganisms are involved in multiple gut and brain functions and metabolic pathways. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Epilepsy
- How many people
- 20 participants
- Where
- 1 siteGreece
- Study dates
- 18 Dec 2019to 31 Dec 2024
- Phase
- Observational
- 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 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children with epilepsy visiting Pediatric Neurology Department of 3rd Pediatric Clinic, Attikon Athens University Hospital
Who may be able to join
- type of epilepsy requiring ketogenic diet (drug-resistant epilepsy or Glut 1 DS or PDHD)
- eligibility for ketogenic diet according to ILAE
- no antibiotic intake for at least 2 months before the beginning of the study
- no probiotics or prebiotics intake for at least 2 weeks before the beginning of the study
Who cannot join
- systematic diseases (e.g. inflammatory bowel disease, cancer, autoimmune and cardiometabolic diseases)
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
Attikon Athens University Hospital
Athens, Haidari, 12462
Sofia D Zouganeli, 00306979147890, szouganeli@attikonhospital.gr
Sofia D Zouganeli
About this study
The role of human microbiota in neurological disorders via the "microbiota-gut-brain axis" is recently gaining increased attention due to the knowledge that gut microorganisms are involved in multiple gut and brain functions and metabolic pathways. The hypothesis of the present investigation is that changes of gut microbiota and their metabolic products may be a mechanism of the effectiveness of ketogenic diet in epilepsy.
The aim of the present study is to investigate the changes of gut microbiota induced by the ketogenic diet and if certain populations of microorganisms are associated with better seizure control in epileptic children.
This is a non-interventional study that will include epileptic children 2-18 years old eligible for ketogenic diet. The gut microbiome of participants will be examined in stools before and three months after the implementation of an olive oil- based ketogenic diet therapy. One of the participants' parents will also be included providing fecal sample for the examination of gut microbiome.
Read the detailed description
The high-fat, adequate protein, low-carbohydrate ketogenic diet (KD) has successfully been used in the treatment of drug resistant epilepsy (DRE) in children since 1920's. The classical KD, with fat to carbohydrate plus protein ratio of 3 or 4:1, as well as less restrictive forms such as Modified Atkins Diet (MAD) or Low Glycemic Index Therapy (LGIT), have been proved to be effective in reducing seizures more than 50% in many patients with low response to more than two antiepileptic drugs (AEDs). Apart from a great number of epileptic syndromes, metabolic conditions like GLUT I-Glucose Transporter I - Deficiency Syndrome and Pyruvate Dehydrogenase Deficiency Syndrome seem to be especially responsive to KD.
The role of human microbiota in neurological disorders via the "microbiota-gut-brain axis" with gut microorganisms getting involved in multiple gut and brain functions and metabolic pathways has recently gained attention .The changes of gut microbiota by the low carbohydrate and low fibre ketogenic diet seem to have an impact on its effectiveness in epilepsy control. Furthermore, metabolic products of gut microorganisms such as SCFAs, apart from producing energy, are implicated in inflammatory pathways and are directly affected by the low fibre - carbohydrate content of the ketogenic diet.
The small number of studies so far confirm the role of gut microbiome in seizure control without specifying the exact mechanisms yet. The aim of the present study is to further investigate how gut microbiota and the metabolic products of microorganisms are implicated in the effectiveness of ketogenic diet therapy in epileptic children.
The study will include epileptic children 2-18 years old eligible for ketogenic diet according to ILAE. The gut microbiome of participants will be examined at the beginning of the study and three months after following an olive-oil based ketogenic diet therapy. One of the participants' parents will also be included, providing fecal samples for the examination of gut microbiome. A written informed consent will be provided by all the participants or care givers.
This is a prospective, non-interventional study which will be held in the Department of Pediatric Neurology, 3d Pediatric Clinic, Attikon Athens University Hospital, in collaboration with the Department of Nutrition and Dietetics, Harokopio University. The study has received approval by the Ethics Committee and the Scientific Board of the Attikon Athens University Hospital.
- Conditions
- Epilepsy
- Keywords
- ketogenic diet, epilepsy, children, gut microbiota
- Medical subject headings
- Epilepsy
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of epileptic seizures frequency
Recording of number of seizures per week/month Recording the ratio of epileptic seizures change e.g. decrease >50%, decrease 50-90%, decrease >90%
Measured: 3 months
Changes in electroengephalographic activity
Subjective assessment of neurophysiologist depending on the diagnosis of each patient's epileptic syndrome.
Measurement of Spike Wave Index (%) in Electrical Status Epilepticus During Slow-wave Sleep (ESES)
Measured: 3 months
Secondary outcomes (2)
Alterations in gut microbiota
alterations in specific gut microbial populations (quantitative real time PCR)
Measured: 3 months
Changes in gut microbial metabolites
Short Chain Fatty Acids quantification (gas chromatography)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start18 Dec 2019
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Attikon Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Harokopio University
- Responsible party
- Principal investigator, Sofia D. Zouganeli, Attikon Hospital
- Investigators
- Argirios Dinopoulos, Professor, Study chair, 3rd Pediatric Clinic, Attikon Athens University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05898438
- Sponsor's protocol ID
- ΕΒΔ620/30-09-2019
- Status last verified
- Jun 2023
- First submitted
- 10 Apr 2023
- Last updated
- 12 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell. 2018 Jun 14;173(7):1728-1741.e13. doi: 10.1016/j.cell.2018.04.027. Epub 2018 May 24.
PubMed 29804833Xie G, Zhou Q, Qiu CZ, Dai WK, Wang HP, Li YH, Liao JX, Lu XG, Lin SF, Ye JH, Ma ZY, Wang WJ. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World J Gastroenterol. 2017 Sep 7;23(33):6164-6171. doi: 10.3748/wjg.v23.i33.6164.
PubMed 28970732Zhang Y, Zhou S, Zhou Y, Yu L, Zhang L, Wang Y. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res. 2018 Sep;145:163-168. doi: 10.1016/j.eplepsyres.2018.06.015. Epub 2018 Jun 28.
PubMed 30007242Lindefeldt M, Eng A, Darban H, Bjerkner A, Zetterstrom CK, Allander T, Andersson B, Borenstein E, Dahlin M, Prast-Nielsen S. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes. 2019 Jan 23;5(1):5. doi: 10.1038/s41522-018-0073-2. eCollection 2019.
PubMed 30701077Tagliabue A, Ferraris C, Uggeri F, Trentani C, Bertoli S, de Giorgis V, Veggiotti P, Elli M. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study. Clin Nutr ESPEN. 2017 Feb;17:33-37. doi: 10.1016/j.clnesp.2016.11.003. Epub 2016 Dec 18.
PubMed 28361745Gong X, Cai Q, Liu X, An D, Zhou D, Luo R, Peng R, Hong Z. Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets. Microb Pathog. 2021 Jun;155:104899. doi: 10.1016/j.micpath.2021.104899. Epub 2021 Apr 21.
PubMed 33894293Peng A, Qiu X, Lai W, Li W, Zhang L, Zhu X, He S, Duan J, Chen L. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res. 2018 Nov;147:102-107. doi: 10.1016/j.eplepsyres.2018.09.013. Epub 2018 Sep 24.
PubMed 30291996Zouganeli S, Mitsou EK, Yannakoulia M, Intze E, Mountzouris KC, Fessatou S, Attilakos A, Kyriacou A, Dinopoulos A. Gut microbiota shifts and short-chain fatty acids alterations in pediatric epilepsy patients on a Mediterranean ketogenic diet. Epileptic Disord. 2026 May 7. doi: 10.1002/epd2.70269. Online ahead of print.
PubMed 42096323
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Gut Microbiota in Children With Epilepsy Following Ketogenic Diet
- ClinicalTrials.gov ID
- NCT05898438
- Acronym / sponsor ID
- ΕΒΔ620/30-09-2019
- Conditions
- Epilepsy
- Keywords
- ketogenic diet, epilepsy, children, gut microbiota
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Attikon HospitalUniversity, hospital or other
- Collaborators
- Harokopio University
- Study start
- 18 Dec 2019 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 12 Jun 2023 (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.
The role of human microbiota in neurological disorders via the "microbiota-gut-brain axis" is recently gaining increased attention due to the knowledge that gut microorganisms are involved in multiple gut and brain functions and metabolic pathways. The hypothesis of the present investigation is that changes of gut microbiota and their metabolic products may be a mechanism of the effectiveness of ketogenic diet in epilepsy.
The aim of the present study is to investigate the changes of gut microbiota induced by the ketogenic diet and if certain populations of microorganisms are associated with better seizure control in epileptic children.
This is a non-interventional study that will include epileptic children 2-18 years old eligible for ketogenic diet. The gut microbiome of participants will be examined in stools before and three months after the implementation of an olive oil- based ketogenic diet therapy. One of the participants' parents will also be included providing fecal sample for the examination of gut microbiome.
Detailed description
The high-fat, adequate protein, low-carbohydrate ketogenic diet (KD) has successfully been used in the treatment of drug resistant epilepsy (DRE) in children since 1920's. The classical KD, with fat to carbohydrate plus protein ratio of 3 or 4:1, as well as less restrictive forms such as Modified Atkins Diet (MAD) or Low Glycemic Index Therapy (LGIT), have been proved to be effective in reducing seizures more than 50% in many patients with low response to more than two antiepileptic drugs (AEDs). Apart from a great number of epileptic syndromes, metabolic conditions like GLUT I-Glucose Transporter I - Deficiency Syndrome and Pyruvate Dehydrogenase Deficiency Syndrome seem to be especially responsive to KD.
The role of human microbiota in neurological disorders via the "microbiota-gut-brain axis" with gut microorganisms getting involved in multiple gut and brain functions and metabolic pathways has recently gained attention .The changes of gut microbiota by the low carbohydrate and low fibre ketogenic diet seem to have an impact on its effectiveness in epilepsy control. Furthermore, metabolic products of gut microorganisms such as SCFAs, apart from producing energy, are implicated in inflammatory pathways and are directly affected by the low fibre - carbohydrate content of the ketogenic diet.
The small number of studies so far confirm the role of gut microbiome in seizure control without specifying the exact mechanisms yet. The aim of the present study is to further investigate how gut microbiota and the metabolic products of microorganisms are implicated in the effectiveness of ketogenic diet therapy in epileptic children.
The study will include epileptic children 2-18 years old eligible for ketogenic diet according to ILAE. The gut microbiome of participants will be examined at the beginning of the study and three months after following an olive-oil based ketogenic diet therapy. One of the participants' parents will also be included, providing fecal samples for the examination of gut microbiome. A written informed consent will be provided by all the participants or care givers.
This is a prospective, non-interventional study which will be held in the Department of Pediatric Neurology, 3d Pediatric Clinic, Attikon Athens University Hospital, in collaboration with the Department of Nutrition and Dietetics, Harokopio University. The study has received approval by the Ethics Committee and the Scientific Board of the Attikon Athens University Hospital.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children with epilepsy visiting Pediatric Neurology Department of 3rd Pediatric Clinic, Attikon Athens University Hospital
Key inclusion criteria (4 listed)
- type of epilepsy requiring ketogenic diet (drug-resistant epilepsy or Glut 1 DS or PDHD)
- eligibility for ketogenic diet according to ILAE
- no antibiotic intake for at least 2 months before the beginning of the study
- no probiotics or prebiotics intake for at least 2 weeks before the beginning of the study
Key exclusion criteria (1 listed)
- systematic diseases (e.g. inflammatory bowel disease, cancer, autoimmune and cardiometabolic diseases)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change of epileptic seizures frequency
Time frame: 3 months
Recording of number of seizures per week/month Recording the ratio of epileptic seizures change e.g. decrease >50%, decrease 50-90%, decrease >90%
Changes in electroengephalographic activity
Time frame: 3 months
Subjective assessment of neurophysiologist depending on the diagnosis of each patient's epileptic syndrome. Measurement of Spike Wave Index (%) in Electrical Status Epilepticus During Slow-wave Sleep (ESES)
2 secondary outcomes
Alterations in gut microbiota
Time frame: 3 months
Changes in gut microbial metabolites
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Background: PubMed 29804833Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell. 2018 Jun 14;173(7):1728-1741.e13. doi: 10.1016/j.cell.2018.04.027. Epub 2018 May 24.
- Background: PubMed 28970732Xie G, Zhou Q, Qiu CZ, Dai WK, Wang HP, Li YH, Liao JX, Lu XG, Lin SF, Ye JH, Ma ZY, Wang WJ. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World J Gastroenterol. 2017 Sep 7;23(33):6164-6171. doi: 10.3748/wjg.v23.i33.6164.
- Background: PubMed 30007242Zhang Y, Zhou S, Zhou Y, Yu L, Zhang L, Wang Y. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res. 2018 Sep;145:163-168. doi: 10.1016/j.eplepsyres.2018.06.015. Epub 2018 Jun 28.
- Background: PubMed 30701077Lindefeldt M, Eng A, Darban H, Bjerkner A, Zetterstrom CK, Allander T, Andersson B, Borenstein E, Dahlin M, Prast-Nielsen S. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes. 2019 Jan 23;5(1):5. doi: 10.1038/s41522-018-0073-2. eCollection 2019.
- Background: PubMed 28361745Tagliabue A, Ferraris C, Uggeri F, Trentani C, Bertoli S, de Giorgis V, Veggiotti P, Elli M. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study. Clin Nutr ESPEN. 2017 Feb;17:33-37. doi: 10.1016/j.clnesp.2016.11.003. Epub 2016 Dec 18.
- Background: PubMed 33894293Gong X, Cai Q, Liu X, An D, Zhou D, Luo R, Peng R, Hong Z. Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets. Microb Pathog. 2021 Jun;155:104899. doi: 10.1016/j.micpath.2021.104899. Epub 2021 Apr 21.
- Background: PubMed 30291996Peng A, Qiu X, Lai W, Li W, Zhang L, Zhu X, He S, Duan J, Chen L. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res. 2018 Nov;147:102-107. doi: 10.1016/j.eplepsyres.2018.09.013. Epub 2018 Sep 24.
- Derived from this study: PubMed 42096323Zouganeli S, Mitsou EK, Yannakoulia M, Intze E, Mountzouris KC, Fessatou S, Attilakos A, Kyriacou A, Dinopoulos A. Gut microbiota shifts and short-chain fatty acids alterations in pediatric epilepsy patients on a Mediterranean ketogenic diet. Epileptic Disord. 2026 May 7. doi: 10.1002/epd2.70269. Online ahead of print.
- 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.
Argirios Dinopoulos, Professor study chair
3rd Pediatric Clinic, Attikon Athens University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy, run by Attikon Hospital at 1 site in Greece.
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 4 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 12 Jun 2023. 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 Greece. 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 Sofia D Zouganeli (00306979147890, szouganeli@attikonhospital.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of epileptic seizures frequency (time frame: 3 months). The study lists 2 primary outcomes in all. 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 NCT05898438, which also lists 8 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 12 Jun 2023.