Comparison of Microbiome Composition and Biomarkers in Pharmaco Resistant and Pharmaco-Sensitive Epilepsy

The purpose of this study is to determine stool microbiome composition and biomarkers that are differentially abundant and those that are associated with response to treatment (eg, anticonvulsant drugs).

Study Overview

• Status: Withdrawn
• Conditions: Epilepsy in Children; Pharmaco-Resistant Epilepsy

Detailed Description

Recent research suggests that the intestinal microbiota plays a central role in human health, and may play a role in a variety of central nervous system disorders, including seizure susceptibility. The microbiota has been shown to be associated with changes in factors relevant to neurotransmission, including neurotransmitter signaling, synaptic protein expression, long-term potentiation, and myelination. In addition to the microbiota's potential role in general neurotransmission, research suggests that the gut microbiome may differ between patients with pharmaco resistant and pharmaco-sensitive epilepsies. In support of this idea, ketogenic diet has been used as an alternative treatment for those with pharmaco-resistant epilepsy and there are indications of possible direct interactions of anti-epileptic drugs (AEDs) with the intestinal microbiota.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

150 study participants are planned, including approximately 50 pharmaco-resistant study participants, approximately 50 pharmaco sensitive study participants, and approximately 50 sibling controls of the pharmaco-resistant study participants.

Description

Inclusion Criteria:

• Study participant and/or legal representative is willing and able to give informed consent/assent for participation in the study.
• Study participant and/or legal representative is willing and able to comply with all study requirements, in the opinion of the Investigator.
• Study participant is between the ages of 12 and 21, inclusive, at the Screening Visit.
• Study participant resides at home (alone or with family).
• Study participant has a confirmed diagnosis of epilepsy (epilepsy groups only; not applicable to sibling controls).
• Study participant has continued unprovoked seizures despite trials of ≥2 appropriate antiepileptic drugs at therapeutic doses (pharmaco resistant epilepsy group only; not applicable to pharmaco sensitive epilepsy group or sibling controls).

Exclusion Criteria:

• Study participant has monogenic epilepsy.
• Study participant has a neurodegenerative disease, mitochondrial disease, metabolic disease, active central nervous system disease, active autoimmune disease, or active inflammatory bowel disease.
• Study participant is on, or has been on within 30 days prior to the Screening Visit, a ketogenic diet, low glycemic index diet, or modified Atkins diet therapy.
• Study participant has had surgery within 3 months of the Screening Visit.
• Study participant is a resident in a group or hospital setting.
• Study participant requires the use of a g-tube or formula feeding.
• Study participant has had antibiotic therapy within 60 days prior to the Screening Visit.
• Study participant has participated in the study of an investigational product within 3 months prior to the Screening Visit (or within 5 half lives of the investigational product, whichever is longer) or is currently participating in a study of an investigational product.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Pharmaco-resistant epilepsy (PRE); Pharmaco resistant patients are defined by seizures despite adequate dosing of ≥2 anticonvulsant drugs.
Pharmaco-sensitive epilepsy (PSE); Pharmaco-sensitive patients are defined by no seizures for 6 months.
Sibling control; Sibling of the of the PRE study participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmaco-sensitive (PSE) vs. pharmaco-resistant epilepsy (PRE) defined by no seizures for 6 months, and seizures despite adequate dosing of ≥2 anticonvulsant drugs, respectively	Bacterial species and metabolomic biomarkers that are associated with PRE/PSE are determined.	24 months

Collaborators and Investigators

• Sponsor: Senda Biosciences
• Collaborators: Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 15, 2020
• Primary Completion (Anticipated): September 15, 2021
• Study Completion (Anticipated): March 15, 2022

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 16, 2020

Study Record Updates

• Last Update Posted (Actual): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: E-NEU-EPY-02

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