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
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.
Show all 10Show fewer
- 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