- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05651204
GABA Biomarkers in Dravet Syndrome
December 13, 2022 updated by: Cook Children's Health Care System
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 Type
Observational
Enrollment (Anticipated)
36
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Sabrina Shandley, PhD
- Phone Number: (682) 885-3437
- Email: Sabrina.Shandley@cookchildrens.org
Study Locations
-
-
Texas
-
Fort Worth, Texas, United States, 76104
- Recruiting
- Cook Children's Medical Center
-
Contact:
- Sabrina Shandley, PhD
- Phone Number: 682-885-3437
- Email: Sabrina.Shandley@cookchildrens.org
-
Contact:
- Laurie Bailey, PhD
- Phone Number: (682) 885-2488
- Email: laurie.bailey@cookchildrens.org
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Principal Investigator:
- Christos Papadelis, PhD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
No older than 16 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
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).
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Dravet
|
Blood specimens will be collected by a registered phlebotomist according to hospital's specimen collection procedures.
|
Age-Matched Control
|
Blood specimens will be collected by a registered phlebotomist according to hospital's specimen collection procedures.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
GABA Blood Level
Time Frame: Up to 30 minutes
|
GABA levels evaluated by clinical blood draw.
|
Up to 30 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BOLD (Blood oxygenation level dependent) MRI
Time Frame: Up to 1.5 hours
|
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.
|
Up to 1.5 hours
|
MEG
Time Frame: Up to 3 hours
|
We will use the MEG to measure evoked fields and potentials elicited by somatosensory, auditory, and visual stimuli.
|
Up to 3 hours
|
HD-EEG
Time Frame: Up to 90 minutes
|
We will use HD-EEG to measure evoked fields and potentials elicited by somatosensory, auditory, and visual stimuli.
|
Up to 90 minutes
|
TMS
Time Frame: Up to 2 Hours
|
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.
|
Up to 2 Hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Christos Papadelis, PhD, Cook Children's Health Care System
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 8, 2022
Primary Completion (Anticipated)
September 8, 2024
Study Completion (Anticipated)
September 8, 2027
Study Registration Dates
First Submitted
October 7, 2022
First Submitted That Met QC Criteria
December 13, 2022
First Posted (Actual)
December 14, 2022
Study Record Updates
Last Update Posted (Actual)
December 14, 2022
Last Update Submitted That Met QC Criteria
December 13, 2022
Last Verified
December 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2022-051
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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