Epigenetics and Gut Microbiota in Children With Epilepsy (EpiMICRO)

The Potential Impact of the Ketogenic Diet on Epigenetics and Gut Microbiota in Children With Epilepsy

The ketogenic diet is a high-fat, low-carbohydrate diet used in the treatment of epilepsy. The diet can be an efficient treatment option in children with drug resistant epilepsy, with more than 50 % seizure reduction in about 40- 70 % of the patients. However, there is still a lack of knowledge regarding the mechanisms of action, how will respond to the treatment and potential adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Other: Ketogenic diet

Detailed Description

The ketogenic diet is a high-fat, moderate protein, low-carbohydrate diet. It is an internationally established treatment option in children with drug resistant epilepsy. About 40 -70 % of children with drug resistant epilepsy treated with the ketogenic diet achieve > 50 % seizure reduction. However, even though the ketogenic diet has been used in the treatment of epilepsy for almost a Century, little is known about how the dietary treatment reduces seizures and which patients that will respond well. In addition, there is limited knowledge about potential adverse effects of the treatment. This is a prospective study following the patients from 4 weeks before initiating the ketogenic diet and during the treatment. The influence of the dietary treatment on the gut microbiota, epigenetics, quality of life, and adverse effects will be investigated.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kaja K Selmer, PhD; Phone Number: 0047 22 11 77 83; Email: k.k.selmer@medisin.uio.no
• Study Contact Backup: Name: Sigrid Pedersen, MSc; Phone Number: 004767501491; Email: ketoprosjekt@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University Hospital
    • Contact: Sigrid Pedersen, MSc; Phone Number: 004767501491; Email: ketoprosjekt@ous-hf.no
    • Contact: Kaja K Selmer, PhD; Phone Number: 004722117783; Email: k.k.selmer@medisin.uio.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Drug resistant epilepsy
• Age 2- 17 years
• Two or more countable seizures/week
• Willing to try treatment with the ketogenic diet for at least 12 weeks

Exclusion Criteria:

• Glucose transporter protein 1 deficiency, pyruvate dehydrogenase deficiency, or pyruvate carboxylase deficiency
• Known or suspected disease in wich the diet is contraindicated
• Epilepsy surgery the last 6 months before diet initiation
• Steroid medications the last 2 months before diet initiation
• Breastfeeding
• Psychogenic non-epileptic seizures
• Eating disorder
• Pregnancy or planed pregnancy
• Feeding disabilities not compatible with dietary treatment
• Inability to follow study scheme
• Previous treatment with high-fat, low- carbohydrate diet
• Medical need to start dietary treatment immediately

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Ketogenic diet; The patients follow the ordinary treatment protocol for initiation and follow-up of the ketogenic diet	Other: Ketogenic diet; The patients follow the ordinary treatment protocol for ketogenic diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the gut microbiota	Changes in the gut microbiota composition in fecal samples from baseline to 12 weeks of dietary treatment will be measured by 16S rRNA analysis.	From baseline to 12 weeks of dietary treatment.
Characterization of DNA methylation	Changes in the DNA methylation in white blood cells from baseline to 12 weeks of dietary treatment will be analyzed using the Infinium Methylation EPIC Kit.	From baseline to 12 weeks of dietary treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in parental quality of life and parental perceptions of their child's quality of life	The impact of the dietary treatment on quality of life will be examined by using a questionaire before and after 12 weeks of dietary treatment. The quality of life score is a parental measure of the impact for the family, based on their hopes and expectations of the effects of the ketogenic diet.The quality of life is rate on a scale from 0 to 10 (0 = quality of life is poor, 10 = quality of life is very good)	12 weeks of dietary treatment.
Adverse effects	To identify potential adverse effects induced by the dietary treatment measured by a structured interview.	12 weeks of dietary treatment.

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo; Lund University; Norwegian University of Life Sciences
• Investigators: Principal Investigator: Kaja K Selmer, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 15, 2017
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): November 1, 2022

Study Registration Dates

• First Submitted: November 11, 2018
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (ACTUAL): August 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: 2016/2016/REK sør-øst

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No