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Cannabis Extract in Refractory Epilepsy Study (CERES)

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ClinicalTrials.gov Identifier: NCT03808935
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : January 21, 2019
Sponsor:
Collaborators:
Ontario Brain Institute
University of Toronto
University Health Network, Toronto
London Health Sciences Centre
MedReleaf
Information provided by (Responsible Party):
The Epilepsy Research Program of the Ontario Brain Institute

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.

Condition or disease Intervention/treatment Phase
Drug Resistant Epilepsy Drug: Medical Cannabis Drug: Placebo Phase 3

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Parallel-Group Study of Cannabidiol Plus Tetrahydrocannabinol (CBD+THC) Given as Adjunctive Therapy in Patients With Refractory Seizures
Actual Study Start Date : January 10, 2019
Estimated Primary Completion Date : January 10, 2021
Estimated Study Completion Date : January 10, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Medical cannabis
Capsules containing cannabis extract, dissolved in high-oleic sunflower oil, and CBD/THC in a 16:1 ratio.
Drug: Medical Cannabis
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.
Other Name: CBD/THC

Placebo Comparator: Placebo Control

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
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.




Primary Outcome Measures :
  1. Frequency of convulsive seizures [ Time Frame: 0 - 10 weeks ]

Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by the adverse events questionnaire [ Time Frame: 0- 10 weeks ]
  2. Changes in blood levels of CBD and THC from baseline to end of treatment [ Time Frame: 0 - 10 weeks ]
  3. Changes in blood levels of AEDs from baseline to end of treatment [ Time Frame: 0 - 10 weeks ]
  4. Changes in blood levels of liver enzymes AST, ALT, and GGT from baseline to end of treatment [ Time Frame: 0 - 10 weeks ]
  5. Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life in Epilepsy Inventory (QOLIE-31) questionnaire [ Time Frame: 0 - 10 weeks ]
    QOLIE-31 is a 31-item measure assessing health-related quality of life in adults with epilepsy. Seven scales assess seizure worry, overall quality of life, emotional well-being, cognitive and medication effects, and social function.

  6. Changes in quality of life from baseline to end of treatment as assessed by the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire [ Time Frame: 0 - 10 weeks ]
    WHOQOL-BREF is a 26-item measure of physical health, psychological health, social relationships, and environment.

  7. Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life Childhood Epilepsy (QOLCE) questionnaire [ Time Frame: 0 - 10 weeks ]
    QOLCE is a 55-item scale assessing health-related quality of life in children with epilepsy from the perspective of the parent or caregiver. It covers cognitive, emotional, social, and physical functioning.

  8. Changes in symptoms of depression from baseline to end of treatment as assessed by the Neurological Disorder Depression Inventory for Epilepsy (NDDI-E) [ Time Frame: 0 - 10 weeks ]
    NDDI-E is a 6-item questionnaire designed to screen for depression in adults with epilepsy.

  9. Changes in symptoms of depression from baseline to end of treatment as assessed by the Quick Inventory of Depressive Symptoms (QIDS) [ Time Frame: 0 - 10 weeks ]
    QIDS is a 16-item measure designed to assess the severity of depressive symptoms.

  10. Changes in symptoms of anxiety from baseline to end of treatment as assessed by the Generalized Anxiety Disorder 7-item (GAD-7) [ Time Frame: 0 - 10 weeks ]
    GAD-7 is a 7-item questionnaire assessing severity of generalized anxiety disorder.

  11. Change in overall severity of epilepsy from baseline to end of treatment as assessed by the Global Analysis of Severity of Epilepsy Scale (GASE) [ Time Frame: 0 - 10 weeks ]
    GASE is a single-item, 7-point global rating scale that was designed to assess the overall severity of epilepsy.

  12. Change in quality of sleep from baseline to end of treatment as assessed by the Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 0 - 10 weeks ]
    PSQI is a 19-item measure assessing subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction.

  13. Change in participant's impression of change from baseline to end of treatment as assessed by the Patients' Global Impression of Change (PGIC) scale [ Time Frame: 0 - 10 weeks ]
    PGIC is a 7-point scale assessing the patient's perspective of overall improvement and efficacy of treatment. Scores range from "very much improved" to "very much worse".

  14. Change in caregiver's impression of change from baseline to end of treatment as assessed by the Caregiver's Global Impression of Change (CGIC) scale [ Time Frame: 0 - 10 weeks ]
    CGIC is a 7-point scale assessing the caregiver's perspective of overall improvement and efficacy of treatment. Scores range from "very much improved" to "very much worse".

  15. Changes in psychological symptoms from baseline to end of treatment as assessed by the Brief Symptom Inventory (BSI-53) [ Time Frame: 0 - 10 weeks ]
    BSI-53 is a 53-item measure assessing psychological profiles. It covers 9 primary domains: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism.

  16. Changes in functional impairment from baseline to end of treatment as assessed by the Sheehan Disability Scale (SDS) [ Time Frame: 0 - 10 weeks ]
    SDS is a 5-item measure assessing functional impairment in three inter-related domains: work/school, social, and family life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03808935


Contacts
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Contact: Clinical Research Coordinator clinicaltrials@eplink.ca

Locations
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Canada, Ontario
University Hospital Campus, London Health Sciences Centre Not yet recruiting
London, Ontario, Canada
Contact: Clinical Research Coordinator       clinicatrials@eplink.ca   
Principal Investigator: Seyed Mirsattari, MD         
University Health Network - Toronto Western Hospital Recruiting
Toronto, Ontario, Canada
Contact: Clinical Research Coordinator       clinicaltrials@eplink.ca   
Principal Investigator: Peter Tai, MD         
Sub-Investigator: Nancy Mingo, MD         
Sub-Investigator: Danielle Andrade, MD         
Sponsors and Collaborators
The Epilepsy Research Program of the Ontario Brain Institute
Ontario Brain Institute
University of Toronto
University Health Network, Toronto
London Health Sciences Centre
MedReleaf
Investigators
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Principal Investigator: 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

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Responsible Party: The Epilepsy Research Program of the Ontario Brain Institute
ClinicalTrials.gov Identifier: NCT03808935     History of Changes
Other Study ID Numbers: EPL29
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Epilepsy Research Program of the Ontario Brain Institute:
epilepsy
drug resistant
refractory
seizures
cannabidiol
cbd
cannabis

Additional relevant MeSH terms:
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Epilepsy
Drug Resistant Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases