Measuring GABA Levels in Children with Dravet Syndrome

Electrophysiological Biomarkers of GABA Metabolism in Children With SCN1A+ Dravet Syndrome

This study is trying to measure GABA levels in the brains of children with Dravet Syndrome to see how they compare to kids without the condition, hoping to find new ways to understand and treat the syndrome.

Quick facts

• Study type: Observational
• Enrollment: 36 (estimated)
• Ages: N/A to 18 Years
• Sex: All
• Sponsor: Cook Children's Health Care System (Academic / other)
• Locations: 1 site (Fort Worth, Texas)
• Trial ID: NCT05651204 on ClinicalTrials.gov

What this trial studies

This observational study aims to non-invasively measure GABA levels in the brains of children with SCN1A+ Dravet Syndrome and compare them to neurodeveloping children. Using evoked and induced cortical responses, the study will correlate these measurements with blood GABA levels and BOLD responses. The goal is to develop noninvasive biomarkers that can help understand the GABA-related pathophysiology in Dravet Syndrome and potentially inform future treatments targeting GABA modulation.

Who should consider this trial

Good fit: Ideal candidates include children aged 0 to 18 years with a confirmed pathogenic SCN1A mutation and a history of normal development prior to the onset of seizures.

Not a fit: Patients who do not have a confirmed SCN1A mutation or those with developmental issues prior to seizure onset may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better understanding and monitoring of GABA levels in children with Dravet Syndrome, potentially guiding future treatment strategies.

How similar studies have performed: While the approach of measuring GABA levels in this manner is innovative, similar studies have shown promise in correlating brain activity with neurotransmitter levels, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Authorized representative (parent/caregiver) must be willing and able to give informed consent for the participant's participation in the study. Participants capable of providing informed assent must be willing to provide their assent.
2. Participant and their parent/caregiver are willing and able (in the PI's opinion) to comply with all study requirements.
3. Participant is male or female aged between 0 months and 18 years of age, inclusive, at the time of consent.
4. Participant has a confirmed pathogenic or likely pathogenic SCN1A mutation, as demonstrated by genetic testing.
5. Participant had normal development prior to onset of first seizure as defined by the Centers 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, or status epilepticus between age 3 and 5 months, inclusive.
7. Participant should have an evaluation by a pediatric neurologist with a diagnosis of DS.

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 a seizure-associated gene besides SCN1A.
4. Participant has a confirmed mutation in a gene besides SCN1A, that is known to increase 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 to seizure onset, by physician report.
7. Participant has a known central nervous system structural abnormality as found on magnetic resonance imaging or computed tomography scan of brain which, in the opinion of the Principal Investigator (PI), is not consistent with the clinical phenotype of DS. Note: Prior scans may be used, and no new scan is required to confirm normal imaging.
8. Metal implants.
9. Baclofen pump.
10. Inability or unwillingness of patient or parent/legally authorized representative to give written informed consent (and/or assent as appropriate).

Where this trial is running

Fort Worth, Texas

• Cook Children's Medical Center — Fort Worth, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Christos Papadelis, PhD — Cook Children's Health Care System
• Study coordinator: Sabrina Shandley, PhD

Conditions Dravet Syndrome