Drug Resistant Epilepsy
Conditions
Keywords
adult and children, cannabis, DRE, CBD-isolate, CBD-enriched Cannabis Herbal Extract (CHE), cannabidiol
Brief summary
Epilepsy is a neurological disorder affecting more than 50 million people globally, including more than 260,000 Canadians. Cannabidiol (CBD) reduces seizure frequency and improves quality of life for adults and children with Drug Resistant Epilepsy (DRE). Several uncontrolled, small, open label studies reported that CBD-enriched Cannabis Herbal Extract (CHE) resulted in a reduction of seizure frequency, but we lack critical information on efficacy, comparative effectiveness and dosing of CBD and ∆9-tetrahydrocannabinol (THC) in children and adults with DRE. CAN-DRE is an early phase, triple-blind, placebo-controlled, randomized clinical trial to answer the questions of if cannabinoids work to reduce seizures in children and adults (24 months to 55 years) with DRE and if CBD works better in an isolate or in a CBD-enriched Cannabis Herbal Extract. The primary outcome of CAN-DRE is reported monthly seizure count from baseline to maintenance phase.
Interventions
DRUGPlacebo
Placebo arm: participants will receive Placebo MPL-012 oil only through the trial participation. MPL-012 is produced by MediPharm Labs, each mL contains 0mg CBD and 0mg THC.
DRUGCBD Isolate
CBD Isolate: MPL-015 is a CBD isolate, produced by MediPharm Labs, each mL contains 100mg CBD and 0mg THC.
DRUGCBD CHE
CBD-CHE arm: MPL -016 is a CBD-enriched cannabis herbal extract, produced by MediPharm Labs, each mL contains 100mg of CBD and 3mg of THC.
Sponsors
University of Manitoba
Canadian Institutes of Health Research (CIHR)
Research Manitoba
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
an early phase, triple-blind, placebo-controlled, randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
24 Months to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 24 months to 55 years old at the time of enrollment 2. Diagnosed with DRE: not achieved seizure freedom, with adequate trials of 2 antiseizure medications 29 3. Medical history of 4 + clinically recognizable seizures (any type with clusters counted as a single event) per month 4. Have a negative pregnancy test at screening for patients who have experienced menarche 5. Agree to abstain from driving and recreational cannabis use throughout the study
Exclusion criteria
1. Diagnosis of psychogenic non-epileptic seizure 2. Recent (\<30 days) change in anticonvulsant therapies including anticonvulsant medications, or settings on vagal nerve stimulator 3. Ketogenic diet started within 6 months (participants stable on the ketogenic diet for more than 6 months are eligible to participate) 4. Vagal nerve stimulator implanted and activated within 12 months 5. Concomitant regular use of narcotics (except in emergencies and physician supervised) 6. Initiation or dosage change of oral or injected steroids within 3 months 7. Allergy or intolerance to compounds in trial preparations 8. DRE secondary to progressive neurological disease 9. Clinically significant cardiac, renal or hepatic disease (as assessed by site investigator); elevated liver enzymes (GGT and/or AST and/or ALT) or lipase \>3 times upper limit, adjusted for age 10. History of psychotic disorders 11. Uncontrolled (in the perspective of the qualified investigator) medical conditions including substance use disorders 12. History or concurrent cannabis use disorder 13. Unwilling or unable to use highly effective methods of contraception throughout the study period and three months post-trial, where applicable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy in reducing seizure frequency | 116 days | reported monthly seizure count from baseline to maintenance |
| Cannabinoid-related AEs and DLTs | 116 + 60 days | The frequency and type of adverse events and dose limiting toxicities (DLTs) reported by caregivers and participants throughout the trial participation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| participant/family acceptability of this trial design | 116 days | to be measured via post-study questionnaire, open-ended questions asked, no specific scale is used. |
| Quality of Life reported by adult participant/family | 116 days | Quality of Life in Epilepsy Inventory (QOLIE-31) tool for adult participants. Changes from baseline to maintenance phase will be compared to measure the outcome. |
| health resource utilization and changes | 176 days | A trial-specific Health Resource Utilization Questionnaire (HRUQ) is used to collect epilepsy participants' healthcare resource usage and out-of-pocket healthcare expenses during trial participation. The data will be analyzed descriptively to measure direct and indirect healthcare resource utilization related to the intervention from baseline phase to 60-day follow up post study protocolized treatment. |
| changes in work and activity impairment affected by seizure | 116 days | WPAI (Work Productivity and Activity Impairment Questionnaire) asks about the effect of participant's seizure on their/their caregivers' ability to work and perform regular activities. Changes reported from baseline to maintenance phase will be compared. |
| Quality of Life reported by pediatric participants and family | 116 days | Quality of Life in Childhood Epilepsy (QOLCE-55) tool for pediatric participants (4 - 17 yrs). Changes from baseline to maintenance phase will be compared to measure the outcome. |
Contacts
CONTACTLauren Kelly, PhD
Outcome results
None listed