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

June 1, 2023 updated by: Sofia D. Zouganeli, Attikon Hospital

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.

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Greece
    • Haidari
      • Athens, Haidari, Greece, 12462
        • Recruiting
        • Attikon Athens University Hospital
        • Contact:
        • Principal Investigator:
          • Sofia D Zouganeli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Children with epilepsy visiting Pediatric Neurology Department of 3rd Pediatric Clinic, Attikon Athens University Hospital

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%
3 months
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)
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alterations in gut microbiota
Time Frame: 3 months
alterations in specific gut microbial populations (quantitative real time PCR)
3 months
Changes in gut microbial metabolites
Time Frame: 3 months
Short Chain Fatty Acids quantification (gas chromatography)
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Attikon Hospital

Collaborators

Harokopio University

Investigators

  • Study Chair: Argirios Dinopoulos, Professor, 3rd Pediatric Clinic, Attikon Athens University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2019

Primary Completion (Estimated)

December 31, 2023

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

April 10, 2023

First Submitted That Met QC Criteria

June 1, 2023

First Posted (Actual)

June 12, 2023

Study Record Updates

Last Update Posted (Actual)

June 12, 2023

Last Update Submitted That Met QC Criteria

June 1, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ΕΒΔ620/30-09-2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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