GABA Biomarkers in Dravet Syndrome

Last updated: December 13, 2022
Sponsor: Cook Children's Health Care System
Overall Status: Active - Recruiting

Phase

N/A

Condition

Seizure Disorders (Pediatric)

Unverricht-lundborg Syndrome

Dravet Syndrome

Treatment

N/A

Clinical Study ID

NCT05651204
2022-051
  • Ages < 18
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

This study will non-invasively obtain levels of GABA in the brain of children with SCN1A+DS and neurodeveloping children through evoked and induced cortical responses, correlate them with the BOLD responses, and with the levels of GABA in their blood.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Authorized representative (parent/caregiver) must be willing and able to give informedconsent for the participant's participation in the study. Participants capable ofproviding informed assent must be willing to provide their assent.
  2. Participant and their parent/caregiver are willing and able (in the PI's opinion) tocomply with all study requirements.
  3. Participant is male or female aged between 0 months and 18 years of age, inclusive, atthe time of consent.
  4. Participant has a confirmed pathogenic or likely pathogenic SCN1A mutation, asdemonstrated by genetic testing.
  5. Participant had normal development prior to onset of first seizure as defined by theCenters for Disease Control and Prevention (CDC 2019).
  6. Participant had an onset of seizures, defined as first focal clonic/hemiclonic,generalized/focal, generalized tonic-clonic/clonic, atonic, prolonged seizure, orstatus epilepticus between age 3 and 5 months, inclusive.
  7. Participant should have an evaluation by a pediatric neurologist with a diagnosis ofDS.

Exclusion

Exclusion Criteria:

  1. Participant has a copy number variant of SCN1A, including SCN1A microdeletion,affecting other genes.
  2. Participant has an SCN1A mutation present on both alleles.
  3. Participant has a known pathogenic or clinically suspected mutation in aseizure-associated gene besides SCN1A.
  4. Participant has a confirmed mutation in a gene besides SCN1A, that is known toincrease the severity of the seizure phenotype.
  5. Participant has a known gain-of-function mutation, as defined by functional studies,including p.Thr226Met.
  6. Participant has a history of notable developmental deficit that was evident prior toseizure onset, by physician report.
  7. Participant has a known central nervous system structural abnormality as found onmagnetic resonance imaging or computed tomography scan of brain which, in the opinionof the Principal Investigator (PI), is not consistent with the clinical phenotype ofDS. Note: Prior scans may be used, and no new scan is required to confirm normalimaging.
  8. Metal implants.
  9. Baclofen pump.
  10. Inability or unwillingness of patient or parent/legally authorized representative togive written informed consent (and/or assent as appropriate).

Study Design

Total Participants: 36
Study Start date:
September 08, 2022
Estimated Completion Date:
September 08, 2027

Study Description

Epileptic seizures may result from too much excitation or too little inhibition in the area in which abnormal discharges start. Excitation and inhibition of neurons are mediated by g-aminobutyric acid (GABA) neurotransmitter among others. Several lines of evidence indicate an abnormal pathophysiological mechanism of GABA in children with Dravet Syndrome (DS). Other studies show that measures of the beta and gamma brain activity with non-invasive electrophysiological techniques correlate with the levels of GABA in the human brain. Here, we propose to assess these measures in children with SCN1A+DS and neurodeveloping healthy controls aiming to develop noninvasive biomarkers for the monitoring of the levels of GABA in their brain. Such a biomarker would be useful for understanding the pathophysiological GABA mechanism in children with DS and potentially guide the development of future GABAergic modulation treatments.

Connect with a study center

  • Cook Children's Medical Center

    Fort Worth, Texas 76104
    United States

    Active - Recruiting

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