Cannabis Extract in Refractory Epilepsy Study (CERES)

The Epilepsy Research Program of the Ontario Brain Institute

Status and phase: Terminated; Phase 3

Conditions: Drug Resistant Epilepsy

Treatments: Drug: Medical Cannabis; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03808935

EPL29

Details and patient eligibility

About

The purpose of this study is to examine whether a low dose of CBD+THC will decrease the frequency of convulsive seizures in adults with drug-resistant epilepsy, when used in addition to standard anti-epileptic drugs (AEDs). This study will also study the genes associated with epilepsy and whether different epileptic syndromes respond to treatment with CBD+THC.

Full description

Background: Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two major compounds found in the cannabis plant. Reports from patients, families, and the scientific community suggest that CBD (when used as an add-on therapy) decreases the number of convulsive seizures in children and adults with Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous sclerosis complex.

Trial design: Phase III, double-blind, randomized, placebo-controlled, parallel-group trial, followed by an open phase where treatment allocation will be revealed and all participants will either continue or begin receiving the active study drug.

Participants: Adults (18 years of age and older) with drug-resistant epilepsy, including patients with Dravet and Lennox Gastaut syndromes, and patients with frequent convulsive seizures (e.g., tonic, tonic-clonic, atonic, drop attacks, and focal motor seizures).

Interventions: Capsules containing a ratio of 16 CBD: 1 THC oil at a maximum total daily dose of approximately 300 mg of CBD per day, divided into equal doses in the morning and evening.

Comparator: Placebo capsules containing high-oleic sunflower oil and no active or medicinal ingredients.

Outcomes: Frequency of seizures; side effects; blood levels of AEDs, CBD, THC, and liver enzymes; impact on cognition and quality of life; genetics.

Sample size: A total of 80 participants (40 assigned to treatment and 40 to control group) recruited from Toronto Western Hospital in Toronto, and University Hospital in London, Ontario.

Time: Each participant will be enrolled for approximately 16 to 18 weeks, while the clinical trial is expected to take place over a period of two years.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of epilepsy according to the ILAE classification.
• At least 4 motor seizures per month at the start of the study, despite treatment with at least two different anti-epileptic drugs (given concurrently or sequentially) for at least one year.
• At least 4 motor seizures per month during the prospective baseline phase (4 weeks) with no 21-day seizure free periods.
• Stable dose(s) of the same AED(s) for one month prior to screening.
• Agrees not to take any cannabinoids during the study or any other investigational compound for one month before the study or outside cannabinoids during the study.
• Is planning to stay in Canada for the duration of the trial.
• Is able to travel to one of the study sites for in-person visits with the study physicians and to a local lab for blood collection.
• Has access to telephone, computer, and internet for regular correspondence and to complete the study questionnaires.

Exclusion criteria

• Participation in a study involving administration of an investigational compound within one month of Visit 1.
• Evidence of clinically significant non-epileptic disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic, or renal disease, etc.) that in the opinion of the investigators could affect the patient's safety or trial conduct.
• Progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
• Occurrence of psychogenic seizures in the previous year.
• History of drug misuse/abuse (other than cannabinoids). Consideration may be given to allowing inclusion of subjects with remote history of drug abuse (within a defined relevant time period).
• Multiple drug allergies (dermatological, hematological, or organ toxicity) or more than one severe drug reaction(s).
• Pregnancy, breastfeeding.
• Known or suspected hypersensitivity to cannabinoids, or any of the excipients of the investigational medicinal product.
• Patients with a history of major depression, suicidal ideation or attempted suicide, schizophrenia or any other psychotic disorder, patients with a family history of schizophrenia.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

17 participants in 2 patient groups, including a placebo group

Medical cannabis

Experimental group

Description:

Capsules containing cannabis extract, dissolved in high-oleic sunflower oil, and CBD/THC in a 16:1 ratio.

Treatment:

Drug: Medical Cannabis

Placebo Control

Placebo Comparator group

Description:

Capsules containing a high-oleic sunflower oil, calorie-equated to the active treatment. There will be no active compounds in the placebo treatment. Following treatment with placebo, all participants in this group will begin treatment with medical cannabis.

Treatment:

Drug: Placebo