Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
1 other identifier
observational
6
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started Nov 2020
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 29, 2020
CompletedStudy Start
First participant enrolled
November 2, 2020
CompletedFirst Posted
Study publicly available on registry
November 4, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2022
CompletedMarch 22, 2022
March 1, 2022
2.1 years
October 29, 2020
March 8, 2022
Conditions
Outcome Measures
Primary Outcomes (4)
Resting motor threshold (% machine output)
Resting motor threshold (rMT) is obtained by single-pulse TMS and measures voltage-gated sodium-channel-mediated cortical excitability. It is the minimum intensity of stimulation needed to reliably evoke a motor evoked potential (MEP) of at least 50 microvolts in over 50% of trials. It is reported as a percentage of total machine output.
1 year
Durations of cortical silent period (ms)
Cortical Silent Period (CSP) is a single-pulse TMS measure of GABA-mediated cortical inhibition, in which stimulation is applied to the motor cortex while subjects are activating a target muscle (here, abductor pollicis brevis and deltoid muscles), resulting in a pause in muscle contraction. The time between stimulation and the return of voluntary muscle activity is the CSP, measured in milliseconds (ms).
1 year
Ratio of motor evoked potential amplitudes (no units)
Facilitation (ICF) are paired-pulse TMS metrics of cortical inhibition and excitability, respectively. A short interval interstimulus (1-5 ms) leads to cortical inhibition reflective of GABAergic neurotransmission; a longer interval interstimulus of 10-20 ms leads to a cortical facilitation, which reflects glutamatergic neurotransmission; an even longer interstimulus interval of 50-300 ms reflects GABAB-mediated local inhibition and likely GABAA-mediated network inhibition. The ratio of the peak-to-peak amplitude (in mm) of the second MEP to the first (or control) MEP will be calculated for each of these stimulation protocols.
1 year
Cortical Inhibitory Tone
Power in the gamma (30-80 Hz) frequency band.
1 year
Study Arms (1)
Subject with DS
Participants will complete two visits spaced out by 4 - 8 weeks to undergo neurophysiological assessments (Electroencephalogram \[EEG\], and Transcranial magnetic stimulation \[TMS\]).
Interventions
Transcranial magnetic stimulation (TMS) is a method for noninvasive electrical cortical stimulation, where small intracranial currents are generated by a powerful, fluctuating, extracranial magnetic field. TMS is unique in its capacity for experimental, diagnostic, and therapeutic utility. Single pulse (spTMS) and paired-pulse TMS (ppTMS) have been used extensively to study, measure, and modulate cortical excitability and plasticity.
These will be an ambulatory EEG recordings that span 24 hours and done without sedation. Recordings will be performed using electrode locations specified by the international 10-20 system for standard clinical practice.
Eligibility Criteria
Children and adults diagnosed with Dravet Syndrome.
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Boston Children's Hospitallead
- Encoded Therapeuticscollaborator
Study Sites (1)
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alexander Rotenberg, MD, PhD
Boston Children's Hospital
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate, Department of Neurology; Director, Neuromodulation Program; Associate Professor of Neurology, Harvard Medical School
Study Record Dates
First Submitted
October 29, 2020
First Posted
November 4, 2020
Study Start
November 2, 2020
Primary Completion
December 1, 2022
Study Completion
December 1, 2022
Last Updated
March 22, 2022
Record last verified: 2022-03
Data Sharing
- IPD Sharing
- Will not share