Cannabis Extract in Refractory Epilepsy Study

NCT03808935 | Terminated Phase 3

• 1 other identifier: EPL29
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Drug Resistant Epilepsy

Keywords

epilepsy; drug resistant; refractory; seizures; cannabidiol; cbd; cannabis

Outcome Measures

Primary Outcomes (1)

• Frequency of convulsive seizures

  0 - 10 weeks

Secondary Outcomes (16)

• Number of participants with treatment-related adverse events as assessed by the adverse events questionnaire

  0- 10 weeks

• Changes in blood levels of CBD and THC from baseline to end of treatment

  0 - 10 weeks

• Changes in blood levels of AEDs from baseline to end of treatment

  0 - 10 weeks

• Changes in blood levels of liver enzymes AST, ALT, and GGT from baseline to end of treatment

  0 - 10 weeks

• Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life in Epilepsy Inventory (QOLIE-31) questionnaire

  0 - 10 weeks

Study Arms (2)

Medical cannabis

EXPERIMENTAL

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

Drug: Medical Cannabis

Placebo Control

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Medical Cannabis DRUG

The experimental intervention will begin with two weeks of titration (100 mg to 200 mg of CBD per day), followed by four weeks of treatment (maximum 300 mg of CBD per day) and four weeks of maintenance (maximum 300 mg of CBD per day). A two week washout phase will slowly decrease the daily dose (200 mg to 100 mg of CBD per day). All daily doses are equally divided into a morning and evening dose.

Also known as: CBD/THC

Medical cannabis

Placebo DRUG

The placebo intervention will begin with two weeks of titration, followed by four weeks of treatment. Participants will then be unblinded to their study group and begin two weeks of titration, four weeks of treatment, and two weeks of washout with medical cannabis, following the same dosing and schedule as the experimental group. All daily doses are equally divided into a morning and evening dose.

Placebo Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The Epilepsy Research Program of the Ontario Brain Institute: lead
• Ontario Brain Institute: collaborator
• University of Toronto: collaborator
• University Health Network, Toronto: collaborator
• London Health Sciences Centre: collaborator
• MedReleaf: collaborator

Study Sites (2)

University Hospital Campus, London Health Sciences Centre

London, Ontario, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Drug Resistant Epilepsy; Epilepsy; Seizures; Color Vision Defects; Marijuana Abuse

Interventions

Medical Marijuana

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vision Disorders; Sensation Disorders; Cone Dystrophy; Eye Diseases, Hereditary; Eye Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• W M Burnham, PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

• Peter Tai, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Seyed Mirsattari, MD

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Nancy Mingo, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Danielle Andrade, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 18, 2019
• Study Start: January 10, 2019
• Primary Completion: March 15, 2020
• Study Completion: March 15, 2020
• Last Updated: September 11, 2020

Record last verified: 2020-09

Locations

CA (2)