Dravet Syndrome
Conditions
Keywords
epilepsy, Sudden Unexpected Death in Epilepsy (SUDEP)
Brief summary
This study investigates cerebrovascular reactivity (CVR) and functional brain connectivity in Dravet Syndrome (DS) patients with convulsive seizures. Using functional MRI (fMRI), we will define differences in brain responses to CO₂ changes before administration of the drug Fintepla (Baseline), with a library of healthy controls and with those obtained after administration of Fintepla (Day \ 60). Changes in CVR and their relation to ventilatory responses will also be assessed during fMRI.
Interventions
DRUGFenfluramine treatment (Fintepla)
Participants will receive Fintepla starting at 0.2 mg/kg/day, up to a maximum of 0.6 mg/kg/day (or 5.9 mL/day, whichever is lower), per FDA guidelines. Dosing will be adjusted as tolerated. After Day \~60, the dose will be gradually tapered.
DEVICEHypercapnia Challenge using the device (RespirAct)
Participants will undergo a hypercapnia challenge using the RespirAct device during fMRI. The protocol includes alternating one minute blocks of controlled CO₂ increases and normocapnia under normoxic conditions.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* DS patients (with or without SCN1A pathogenic mutations) * Generalized convulsive seizures
Exclusion criteria
* known cardiorespiratory, hepatic or renal disease, and/or * allergic reactions or other contraindications to fenfluramine and/or * on Stiripentol treatment, and/or * on serotonergic medications, and/or * contraindications to Midazolam anesthesia * taken the following drugs within 14 days: monoamine oxidase inhibitors (MAOIs), anti-depressants (Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and norepinephrine reuptake inhibitors (SNRIs), and Tricyclic antidepressants (TCAs)), St. John's Wort, Tryptophan, and Dextromethorphan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in blood oxygenation level in response to CO₂ | Baseline, Day ~60 | Measures how much blood oxygenation level dependent (BOLD) signal changes in response to CO₂, using fMRI. |
| Change in speed of cerebrovascular response to CO₂ | Baseline, Day ~60 | Measures how quickly the brain responds to CO₂ exposure during fMRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in breathing response to CO₂ | Baseline, Day ~60 | Assesses how the participant's breathing rate changes when CO₂ levels are increased. |
Countries
United States
Contacts
CONTACTSamden Lhatoo, MD, FRCP
CONTACTSandhya Rani
PRINCIPAL_INVESTIGATORSamden Lhatoo, MD, FRCP
The University of Texas Health Science Center, Houston
Outcome results
None listed