Role of the Gut Microbiota in Pediatric Epilepsy

Study Overview
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Brief Summary
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Nearly a third of children with epilepsy are refractory to pharmacotherapy. The ketogenic diet (KD) is a highly effective alternative therapy reducing seizure frequency by 50% in more than half of treated children. The exact mechanisms of KD remain poorly understood, and recent studies have implicated the gut microbiota (GM). This pilot study aims to determine the feasibility of a 12-week dietary intervention with prebiotic fiber in children with epilepsy. The investigators hypothesize that consumption of inulin will alter gut microbiota and may have effects on seizure frequency.

Official Title
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Leveraging the Gut Microbiota in Pediatric Refractory Epilepsy: Safety and Feasibility of Oligofructose-enriched Inulin Supplementation for Dysbiosis and Seizure Control

Conditions
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Drug Resistant Epilepsy

Intervention / Treatment
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* Dietary Supplement: Prebiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with epilepsy: Age 2-18. Attended the epilepsy clinic for a minimum of 6 months. On a stable number and type of medications for 4 weeks. Have not previously been on the ketogenic diet. Healthy controls: Aged 2-18. Immunocompetent. No medical comorbidities (e.g. autoimmune, metabolic, cardiovascular, renal, or gastrointestinal conditions). Exclusion Criteria: Health conditions such as disorders of fatty acid transport and oxidation, porphyria, and pancreatitis, Glucose transporter 1 deficiency, pyruvate dehydrogenase deficiency, diabetes, and other autoimmune diseases. Presence of HIV infection, chronic wound infection, or osteomyelitis Presence of or treatment for periodontal infection Inflammatory bowel disease, chronic diarrhea, current Clostridium difficile infection Treatment with immunosuppressive agents in the past 6 months Significant changes in dietary intake (i.e. excluded sugar, lactose or gluten from their diet, started consuming a vegetarian or vegan diet) over the past 6 months. Gastrointestinal illness in the past month or food intolerances leading to gastrointestinal symptoms. Use of antibiotics in the 3 months preceding the study. Use of probiotic or prebiotic supplements in the month preceding the study. Consumption of probiotic yoghurt in the past 2 weeks. Use of laxatives, proton pump inhibitors, or gastric motility medications in the month preceding the study. History of allergic reaction or intolerance of maltodextrin or inulin.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Maltodextrin 4 grams daily for ≤ age 6; or 8 grams daily for >6 years | Dietary Supplement: Placebo<br>* Maltodextrin 4 grams daily for ≤ age 6; or 8 grams daily for >6 years<br>|
| Experimental: Prebiotic<br>Oligofructose-enriched inulin 4 grams daily for ≤ age 6; or 8 grams daily for >6 years | Dietary Supplement: Prebiotic<br>* Oligofructose-enriched inulin. 4 grams daily for ≤ age 6; or 8 grams daily for >6 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in alpha and beta bacterial diversity measures in stool | Compare the effect of oral inulin vs. placebo on alpha and beta bacterial diversity in the stool of children undergoing ketogenic diet therapy for epilepsy | 12 weeks | 
| Change in Short Chain Fatty Acid (SCFA) levels in stool | Compare the effect of inulin vs. placebo on SCFA levels in the stool of children undergoing ketogenic diet therapy for epilepsy | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure frequency | Trends in seizure frequency during inulin treatment compared to pre-treatment. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketogenic Diet, Gut Microbiome, Inulin