Current Environment:

Summary

Dravet syndrome (DS) is an epileptic encephalopathy caused by pathogenic variants in the SCN1A gene resulting in medically refractory epilepsy and psychomotor delays. As a pilot study assessing for feasibility, the investigators aim to test whether alterations in cortical excitatory:inhibitory ratio can be reliably recorded. The investigators will utilize transcranial magnetic stimulation (TMS) metrics of cortical excitatory and inhibitory tone as an initial step towards translating findings from rodent genetic models of DS into disease-specific biomarkers and offer future measures of therapeutic target engagement in this patient population. Participants will complete two visits, each consisting of a TMS session and an EEG session. Visits will be scheduled 4-8 weeks apart.

Conditions

Dravet Syndrome

Recruitment Status

UNKNOWN

Detailed Description

This is a single site study to be conducted at Boston Children's Hospital (BCH) investigating the neurophysiological biomarkers of epilepsy and developmental disability in children and young adults with Dravet Syndrome. Mechanistically, the features of the DS phenotype are attributable to a loss of cortical inhibition. TMS is a non-invasive form of focal cortical stimulation in which an external powerful magnet induces an electrical field intracranially over the stimulated region that is used to interrogate or modulate states of cortical excitation or inhibition. Accordingly, the investigators propose to test whether metrics of cortical excitability and inhibition can be obtained by transcranial magnetic stimulation (TMS) and EEG in patients with DS.

Eligibility Criteria

Inclusion Criteria:

* Age: 6 months - 30 years
* Ability to obtain informed consent with the participant or legally authorized representative
* DS confirmed by pathogenic variant in SCN1A gene
* Medical history consistent with clinical phenotype of DS

Exclusion Criteria:

* Comorbid conditions such as a second genetic diagnosis which may confound interpretation.
* Current or planned participation in a clinical drug or device trial.
* Previous participation in a gene therapy or gene editing trial
* Allergy to adhesives used for surface EMG electrodes
* Contraindications to TMS (e.g. implanted devices for which there is no TMS safety data)

Intervention

Intervention Type

Intervention Name

DEVICE

Transcranial Magnetic Stimulation (TMS)

DEVICE

Electroencephalogram (EEG)

Gender

ALL

Min Age

6 Months

Max Age

30 Years

Download Date

2022-03-22

Principal Investigator

N/A

Primary Contact Information

Paul MacMullin

617-355-4875

Paul.MacMullin@childrens.harvard.edu

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team:

Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome NCT04614506 Paul MacMullin 617-355-4875 Paul.MacMullin@childrens.harvard.edu Melissa Tsuboyama, MD Melissa.Tsuboyama@childrens.harvard.edu