Role of the Gut Microbiota in Pediatric Epilepsy (EPBiome)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Drug Resistant Epilepsy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Prebiotic

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maksim Parfyonov, MD; Phone Number: 7788635905; Email: info@epbiome.com
• Study Contact Backup: Name: Linda Huh, MD; Email: lhuh@cw.bc.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Not yet recruiting
      • Alberta Children's Hospital
      • Contact: Juan Pablo Appendino, MD; Email: JP.Appendino@albertahealthservices.ca
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Recruiting
      • BC Children's Hospital
      • Contact: Maksim Parfyonov, MD; Email: info@epbiome.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: British Columbia Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 10, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Ketogenic Diet; Gut Microbiome; Inulin
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy
• Other Study ID Numbers: H19-01935

Drug and device information, study documents

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