Dronabinol, Cannabidiol for Refractory epilepsy

Inclusion criteria

• {"criterion_text":"- Minimum age of 1 year old and maximum age of 18 years old.\n- Confirmed diagnosis of refractory epilepsy according to ILAE criteria.\n- At least 4 countable seizures (not all on one day) during the 4-week baseline period while receiving at least 1 ASM.\n- All medications or interventions for epilepsy must have been stable dosed for one month prior to screening and the participant is willing to maintain the current ASM regimen throughout the trial.\n- Informed consent/assent of legal representative/ parents.\n- Presence of a consistently available patient caregiver for proxy-reports."}

Exclusion criteria

• {"criterion_text":"- Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP).\n- History of recreational or medicinal cannabis, or cannabinoid-based medications, within three months prior to screening and the patient is unwilling to abstain for the duration of the study.\n- Planned intervention under general anesthesia interfering with the baseline period; or any planned major surgery within the duration of the trial.\n- Expected inability to undergo blood sampling due to anxiety or resistance.\n- History or current symptoms of significantly impaired liver function, such as bilirubin level ≥ 2 x upper limit of normal; or presence of liver damage as indicated by levels of alanine aminotransferase and/or aspartate aminotransferase ≥ 3 x upper limit of normal.\n- Pregnancy, breastfeeding, or intention to become pregnant throughout the trial or within 3 months of completing treatment.\n- Structural heart disease.\n- Glaucoma.\n- Ongoing evaluation for epilepsy surgery.\n- Implementation of vagal nerve stimulation within 3 months prior to screening and unwillingness to delay inclusion until stable settings of vagal nerve stimulation are reached.\n- Starting a ketogenic diet within 3 months prior to screening and unwillingness to delay inclusion until a stable ketogenic diet is reached.\n- Unstable medical condition(s), other than refractory epilepsy, that are of significant influence on participation in the trial; significance to be determined with the treating physician/pediatric neurologist."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in daily seizure frequency during placebo periods compared to the change from baseline in daily seizure frequency during active treatment periods.","definition_or_measurement_approach":"Comparison of change from baseline in daily seizure frequency between placebo periods and active treatment periods. Baseline defined as the 4-week baseline period during which participants must have at least 4 countable seizures while receiving at least one ASM."}

Secondary endpoints

• {"endpoint_text":"- Change in score from baseline during placebo versus CBD treatment of: Quality of Life in Childhood Epilepsy (QoLCE-55); Global Assessment of Severity of Epilepsy (GASE); Clinical Global Impression of Change (CGI-C); Aberrant Behavior Checklist (ABC); Vineland Adaptive Behavior Score III (VABS-III); Sleep Disturbances Scale for Children (SDSC); Goal attainment scaling (GAS).\n- Number of (serious) adverse events\n- Clinical characteristics including: age; gender; epilepsy characteristics; etiology; comorbidity; co-medication.\n- Measurements of neuronal excitability, measured on EEG and TMS-EMG: assessment of epileptic discharges on EEG; assessment of background activity on EEG; measurement of resting motor threshold on TMS-EMG; measurement of cortical silent period (CSP) on TMS-EMG.\n- Pharmacogenetic assessment of CYP-enzymes such as CYP2C19, CYP2C9, and CYP3A4.\n- Change in productivity loss measured by iMTA Productivity Cost Questionnaire; change in healthcare resources used measured by iMTA Treatment Inventory of Costs in Patients with psychiatric disorders for Children; change in health related quality of life measured by EuroQol Five-Dimensional Questionnaire, Youth version","definition_or_measurement_approach":"Patient-reported and clinician-rated questionnaires and scales as listed (QoLCE-55, GASE, CGI-C, ABC, VABS-III, SDSC, GAS) for score changes; safety assessed by counting adverse events/serious adverse events; clinical characteristics collected descriptively; neuronal excitability measured by EEG and TMS-EMG including specified assessments; pharmacogenetics through CYP enzyme testing (CYP2C19, CYP2C9, CYP3A4); economic and HRQoL outcomes via iMTA questionnaires and EQ-5D Youth version."}

Netherlands

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

31-12-2025

Processing Time Days

566

Number Of Sites

5

Number Of Participants

50

Primary sponsor

Full Name

Universitair Medisch Centrum Utrecht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands