Role of the Gut Microbiota in Pediatric Epilepsy

Phase 4

• Conditions: Drug Resistant Epilepsy
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Prebiotic

• Registration Number: NCT04705298
• Lead Sponsor: British Columbia Children's Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-05
• Study First Submitted QC: 2021-01-10
• Study First Posted: 2021-01-12
• Study Start: 2021-06-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-07
• Last Update Posted: 2022-03-09
• Primary Completion: 2022-09-01
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Children with epilepsy:

  1. Age 2-18.
  2. Attended the epilepsy clinic for a minimum of 6 months.
  3. On a stable number and type of medications for 4 weeks.
  4. Have not previously been on the ketogenic diet.

  • Healthy controls:

    1. Aged 2-18.
    2. Immunocompetent.
    3. No medical comorbidities (e.g. autoimmune, metabolic, cardiovascular, renal, or gastrointestinal conditions).

Exclusion Criteria

1. 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.
2. Presence of HIV infection, chronic wound infection, or osteomyelitis
3. Presence of or treatment for periodontal infection
4. Inflammatory bowel disease, chronic diarrhea, current Clostridium difficile infection
5. Treatment with immunosuppressive agents in the past 6 months
6. 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.
7. Gastrointestinal illness in the past month or food intolerances leading to gastrointestinal symptoms.
8. Use of antibiotics in the 3 months preceding the study.
9. Use of probiotic or prebiotic supplements in the month preceding the study.
10. Consumption of probiotic yoghurt in the past 2 weeks.
11. Use of laxatives, proton pump inhibitors, or gastric motility medications in the month preceding the study.
12. History of allergic reaction or intolerance of maltodextrin or inulin.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Maltodextrin 4 grams daily for ≤ age 6; or 8 grams daily for \>6 years
Prebiotic	Prebiotic	Oligofructose-enriched inulin 4 grams daily for ≤ age 6; or 8 grams daily for \>6 years

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Seizure frequency	12 weeks	Trends in seizure frequency during inulin treatment compared to pre-treatment.

Trial Locations

Locations (2)

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

BC Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada