The Role of Gut Microbiota in Children With Epilepsy Following Ketogenic Diet

NCT ID: NCT05898438

Last Updated: 2023-06-12

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-12-18
• Study Completion Date: 2024-12-31

Brief 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. 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.

Conditions

Epilepsy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• systematic diseases (e.g. inflammatory bowel disease, cancer, autoimmune and cardiometabolic diseases)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Harokopio University

OTHER

Sponsor Role: collaborator

Attikon Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sofia D. Zouganeli

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Argirios Dinopoulos, Professor

Role: STUDY_CHAIR

3rd Pediatric Clinic, Attikon Athens University Hospital

Locations

Attikon Athens University Hospital

Athens, Haidari, Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Sofia D Zouganeli

Role: CONTACT

szouganeli@attikonhospital.gr

00306979147890

Facility Contacts

Sofia D Zouganeli

Role: primary

szouganeli@attikonhospital.gr

00306979147890

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 28970732 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 30007242 (View on PubMed)

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Reference Type: BACKGROUND

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Tagliabue 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.

Reference Type: BACKGROUND

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Gong 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.

Reference Type: BACKGROUND

PMID: 33894293 (View on PubMed)

Peng 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.

Reference Type: BACKGROUND

PMID: 30291996 (View on PubMed)

Other Identifiers

ΕΒΔ620/30-09-2019

Identifier Type: -

Identifier Source: org_study_id