Dravet SyndromeNCT05651204
GABA Biomarkers in Dravet Syndrome
An observational study of Dravet Syndrome, run by Cook Children's Health Care System at 1 site in United States.
Trial summary
This study will non-invasively obtain levels of GABA in the brain of children with SCN1A+DS and neurodeveloping children through evoked and induced cortical responses, correlate them with the BOLD responses, and with the levels of GABA in their blood. Read more about this study
- Who is it for?
- Ages Up to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Dravet Syndrome
- What is being tested?
- GABA Blood Level
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2022to 8 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Up to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: This study will recruit 18 children with a diagnosis of SCN1A+DS and 18 aged-matched neurotypical children (all aged 0-18 years old). Participants will be divided into three different age groups: * 0-7 years old (n=12; 6 children with a diagnosis of SCN1A+ DS and 6 age-matched neurotypical children). * >7-12 years old (n=12; 6 children with a diagnosis of SCN1A+ DS and 6 age-matched neurotypical children). * >12-18 years old (n=12; 6 children with a diagnosis of SCN1A+ DS and 6 age-matched neurotypical children).
Who may be able to join
- 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.
- Participant and their parent/caregiver are willing and able (in the PI's opinion) to comply with all study requirements.
- Participant is male or female aged between 0 months and 18 years of age, inclusive, at the time of consent.
- Participant has a confirmed pathogenic or likely pathogenic SCN1A mutation, as demonstrated by genetic testing.
- Participant had normal development prior to onset of first seizure as defined by the Centers for Disease Control and Prevention (CDC 2019).
- 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.
- Participant should have an evaluation by a pediatric neurologist with a diagnosis of DS.
Who cannot join
- Participant has a copy number variant of SCN1A, including SCN1A microdeletion, affecting other genes.
- Participant has an SCN1A mutation present on both alleles.
- Participant has a known pathogenic or clinically suspected mutation in a seizure-associated gene besides SCN1A.
- Participant has a confirmed mutation in a gene besides SCN1A, that is known to increase the severity of the seizure phenotype.
- Participant has a known gain-of-function mutation, as defined by functional studies, including p.Thr226Met.
- Participant has a history of notable developmental deficit that was evident prior to seizure onset, by physician report.
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- 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.
- Metal implants.
- Baclofen pump.
- Inability or unwillingness of patient or parent/legally authorized representative to give written informed consent (and/or assent as appropriate).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cook Children's Medical Center
Fort Worth, Texas, 76104
Sabrina Shandley, PhD, 682-885-3437, Sabrina.Shandley@cookchildrens.org
Laurie Bailey, PhD, (682) 885-2488, laurie.bailey@cookchildrens.org
About this study
Official title: Electrophysiological Biomarkers of GABA Metabolism in Children With SCN1A+ Dravet Syndrome
This study will non-invasively obtain levels of GABA in the brain of children with SCN1A+DS and neurodeveloping children through evoked and induced cortical responses, correlate them with the BOLD responses, and with the levels of GABA in their blood.
Read the detailed description
Epileptic seizures may result from too much excitation or too little inhibition in the area in which abnormal discharges start. Excitation and inhibition of neurons are mediated by g-aminobutyric acid (GABA) neurotransmitter among others. Several lines of evidence indicate an abnormal pathophysiological mechanism of GABA in children with Dravet Syndrome (DS). Other studies show that measures of the beta and gamma brain activity with non-invasive electrophysiological techniques correlate with the levels of GABA in the human brain. Here, we propose to assess these measures in children with SCN1A+DS and neurodeveloping healthy controls aiming to develop noninvasive biomarkers for the monitoring of the levels of GABA in their brain. Such a biomarker would be useful for understanding the pathophysiological GABA mechanism in children with DS and potentially guide the development of future GABAergic modulation treatments.
- Conditions
- Dravet Syndrome
- Being tested
- GABA Blood Level
- Medical subject headings
- Epilepsies, Myoclonic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GABA Blood LevelDiagnostic test
Blood specimens will be collected by a registered phlebotomist according to hospital's specimen collection procedures.
| Study group | Role | What they receive |
|---|---|---|
| Dravet | Not described Receives: Diagnostic Test: GABA Blood Level | |
| Age-Matched Control | Not described Receives: Diagnostic Test: GABA Blood Level |
What is being measured
The primary outcome is the main question the study is designed to answer.
GABA Blood Level
GABA levels evaluated by clinical blood draw.
Measured: Up to 30 minutes
Secondary outcomes (4)
BOLD (Blood oxygenation level dependent) MRI
For the task-fMRI scans, we will present to the participant child-friendly cartoon images and videos in order to localize the visually-induced BOLD response in their primary visual cortex. We will also deliver compressed air-puffs using a pneumatic stimulator and brush their fingers with a toothbrush in order to localize the somatosensory-induced BOLD response in their primary somatosensory cortex. Lastly, we will deliver to the participant beep sounds through an MRI-compatible headset in order to localize the auditory-induced BOLD response in their primary auditory cortex.
Measured: Up to 1.5 hours
MEG
We will use the MEG to measure evoked fields and potentials elicited by somatosensory, auditory, and visual stimuli.
Measured: Up to 3 hours
HD-EEG
We will use HD-EEG to measure evoked fields and potentials elicited by somatosensory, auditory, and visual stimuli.
Measured: Up to 90 minutes
TMS
TMS is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain in order to map the motor cortex. An electromagnetic coil is placed against the scalp near the forehead. The electromagnet non-invasively delivers a magnetic pulse that stimulates nerve cells in the region of your brain involved in motor control.
Measured: Up to 2 Hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2022
- Study start8 Sep 2022
- Primary completion8 Sep 2024 (estimated)
- Study completion8 Sep 2027 (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.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cook Children's Health Care System
- Sponsor type
- University, hospital or other
- Collaborators
- Encoded Therapeutics
- Responsible party
- Sponsor
- Investigators
- Christos Papadelis, PhD, Principal investigator, Cook Children's Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05651204
- Sponsor's protocol ID
- 2022-051
- Status last verified
- Dec 2022
- First submitted
- 7 Oct 2022
- Last updated
- 14 Dec 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 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiological Biomarkers of GABA Metabolism in Children With SCN1A+ Dravet Syndrome
- ClinicalTrials.gov ID
- NCT05651204
- Acronym / sponsor ID
- 2022-051
- Conditions
- Dravet Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Cook Children's Health Care SystemUniversity, hospital or other
- Collaborators
- Encoded Therapeutics
- Study start
- 8 Sep 2022 (actual)
- Primary completion
- 8 Sep 2024 (estimated)
- Study completion
- 8 Sep 2027 (estimated)
- First posted
- 14 Dec 2022 (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.
This study will non-invasively obtain levels of GABA in the brain of children with SCN1A+DS and neurodeveloping children through evoked and induced cortical responses, correlate them with the BOLD responses, and with the levels of GABA in their blood.
Detailed description
Epileptic seizures may result from too much excitation or too little inhibition in the area in which abnormal discharges start. Excitation and inhibition of neurons are mediated by g-aminobutyric acid (GABA) neurotransmitter among others. Several lines of evidence indicate an abnormal pathophysiological mechanism of GABA in children with Dravet Syndrome (DS). Other studies show that measures of the beta and gamma brain activity with non-invasive electrophysiological techniques correlate with the levels of GABA in the human brain. Here, we propose to assess these measures in children with SCN1A+DS and neurodeveloping healthy controls aiming to develop noninvasive biomarkers for the monitoring of the levels of GABA in their brain. Such a biomarker would be useful for understanding the pathophysiological GABA mechanism in children with DS and potentially guide the development of future GABAergic modulation treatments.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dravet | – | Diagnostic Test: GABA Blood Level |
| Age-Matched Control | – | Diagnostic Test: GABA Blood Level |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- This study will recruit 18 children with a diagnosis of SCN1A+DS and 18 aged-matched neurotypical children (all aged 0-18 years old). Participants will be divided into three different age groups: * 0-7 years old (n=12; 6 children with a diagnosis of SCN1A+ DS and 6 age-matched neurotypical children). * >7-12 years old (n=12; 6 children with a diagnosis of SCN1A+ DS and 6 age-matched neurotypical children). * >12-18 years old (n=12; 6 children with a diagnosis of SCN1A+ DS and 6 age-matched neurotypical children).
Key inclusion criteria (7 listed)
- 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.
- Participant and their parent/caregiver are willing and able (in the PI's opinion) to comply with all study requirements.
- Participant is male or female aged between 0 months and 18 years of age, inclusive, at the time of consent.
- Participant has a confirmed pathogenic or likely pathogenic SCN1A mutation, as demonstrated by genetic testing.
- Participant had normal development prior to onset of first seizure as defined by the Centers for Disease Control and Prevention (CDC 2019).
Key exclusion criteria (10 listed)
- Participant has a copy number variant of SCN1A, including SCN1A microdeletion, affecting other genes.
- Participant has an SCN1A mutation present on both alleles.
- Participant has a known pathogenic or clinically suspected mutation in a seizure-associated gene besides SCN1A.
- Participant has a confirmed mutation in a gene besides SCN1A, that is known to increase the severity of the seizure phenotype.
- Participant has a known gain-of-function mutation, as defined by functional studies, including p.Thr226Met.
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 |
|---|---|---|
| GABA Blood LevelBlood specimens will be collected by a registered phlebotomist according to hospital's specimen collection procedures. | Diagnostic test | Age-Matched Control, Dravet |
Primary outcome
GABA Blood Level
Time frame: Up to 30 minutes
GABA levels evaluated by clinical blood draw.
4 secondary outcomes
BOLD (Blood oxygenation level dependent) MRI
Time frame: Up to 1.5 hours
MEG
Time frame: Up to 3 hours
HD-EEG
Time frame: Up to 90 minutes
TMS
Time frame: Up to 2 Hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 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.
Christos Papadelis, PhD principal investigator
Cook Children's Health Care System
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 Cook Children's Health Care System 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 7 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 14 Dec 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sabrina Shandley, PhD ((682) 885-3437, Sabrina.Shandley@cookchildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GABA Blood Level (time frame: Up to 30 minutes). 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 14 Dec 2022.