Brief Title
Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
Official Title
Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
Brief 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.
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.
Study Type
Observational
Primary Outcome
Resting motor threshold (% machine output)
Condition
Dravet Syndrome
Intervention
Transcranial Magnetic Stimulation (TMS)
Study Arms / Comparison Groups
Subject with DS
Description: Participants will complete two visits spaced out by 4 - 8 weeks to undergo neurophysiological assessments (Electroencephalogram [EEG], and Transcranial magnetic stimulation [TMS]).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Device
Estimated Enrollment
6
Start Date
November 2, 2020
Completion Date
December 2022
Primary Completion Date
December 2022
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)
Gender
All
Ages
6 Months - 30 Years
Accepts Healthy Volunteers
No
Contacts
Alexander Rotenberg, MD, PhD, 617-355-4875, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04614506
Organization ID
IRB-P00034206
Responsible Party
Principal Investigator
Study Sponsor
Boston Children's Hospital
Collaborators
Encoded Therapeutics
Study Sponsor
Alexander Rotenberg, MD, PhD, Principal Investigator, Boston Children's Hospital
Verification Date
March 2022