Epigenetics and Gut Microbiota in Children With Epilepsy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Epilepsy

Intervention / Treatment
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* Other: Ketogenic diet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a prospective, non-randomized study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ketogenic diet<br>The patients follow the ordinary treatment protocol for initiation and follow-up of the ketogenic diet | Other: Ketogenic diet<br>* The patients follow the ordinary treatment protocol for ketogenic diet<br>|

What is the study measuring?
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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. |