Dravet SyndromeNCT04614506
Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
An observational study of Dravet Syndrome, run by Boston Children's Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 months to 30 years
- Conditions the study is for
- Dravet Syndrome
- What is being tested?
- Transcranial Magnetic Stimulation (TMS) and Electroencephalogram (EEG)
- Type of treatment
- Medical device
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2020to Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children and adults diagnosed with Dravet Syndrome.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Melissa Tsuboyama, MD contact
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Paul MacMullin, Paul.MacMullin@childrens.harvard.edu
Alexander Rotenberg, MD, PHD
About this study
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.
Read the 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.
- Conditions
- Dravet Syndrome
- Being tested
- Transcranial Magnetic Stimulation (TMS), Electroencephalogram (EEG)
- Medical subject headings
- Epilepsies, Myoclonic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (TMS)Device
Also called Nexstim Navigated Brain Stimulation (NBS) System 4
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.
Electroencephalogram (EEG)Device
Also called Natus
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.
| Study group | Role | What they receive |
|---|---|---|
| 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]). Receives: Device: Transcranial Magnetic Stimulation (TMS); Device: Electroencephalogram (EEG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 1 year
Cortical Inhibitory Tone
Power in the gamma (30-80 Hz) frequency band.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2020
- Study start2 Nov 2020
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dravet SyndromeStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Encoded Therapeutics
- Responsible party
- Principal investigator, Alexander Rotenberg, Boston Children's Hospital
- Investigators
- Alexander Rotenberg, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04614506
- Sponsor's protocol ID
- IRB-P00034206
- Status last verified
- Mar 2022
- First submitted
- 29 Oct 2020
- Last updated
- 22 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
- ClinicalTrials.gov ID
- NCT04614506
- Acronym / sponsor ID
- IRB-P00034206
- Conditions
- Dravet Syndrome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Encoded Therapeutics
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 4 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subject with DS | – | Device: Transcranial Magnetic Stimulation (TMS), Device: Electroencephalogram (EEG)Participants will complete two visits spaced out by 4 - 8 weeks to undergo neurophysiological assessments (Electroencephalogram [EEG], and Transcranial magnetic stimulation [TMS]). |
Who may qualify
- Ages
- 6 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children and adults diagnosed with Dravet Syndrome.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation (TMS)Also: Nexstim Navigated Brain Stimulation (NBS) System 4Transcranial 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. | Device | Subject with DS |
| Electroencephalogram (EEG)Also: NatusThese 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. | Device | Subject with DS |
Primary outcome
Resting motor threshold (% machine output)
Time frame: 1 year
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.
Durations of cortical silent period (ms)
Time frame: 1 year
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).
Ratio of motor evoked potential amplitudes (no units)
Time frame: 1 year
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.
Cortical Inhibitory Tone
Time frame: 1 year
Power in the gamma (30-80 Hz) frequency band.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa Tsuboyama, MD contact
Alexander Rotenberg, MD, PhD principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dravet Syndrome, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paul MacMullin (617-355-4875, Paul.MacMullin@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting motor threshold (% machine output) (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2022.