Drug Resistant EpilepsyPhase 3CERESNCT03808935

Cannabis Extract in Refractory Epilepsy Study

A Phase 3 study testing Medical Cannabis in people with Drug Resistant Epilepsy, run by The Epilepsy Research Program of the Ontario Brain Institute at 2 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Drug Resistant Epilepsy
What is being tested?: Medical Cannabis
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 17 participants
Where: 2 sitesCanada
Study dates: 10 Jan 2019to 15 Mar 2020
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

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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 locations and contacts

2 sites in 1 country.

Canada2 sites

University Hospital Campus, London Health Sciences Centre
London, Ontario
University Health Network - Toronto Western Hospital
Toronto, Ontario

Other trials in Canada

About this study

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

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.

Read the 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.

Conditions: Drug Resistant Epilepsy
Being tested: Medical Cannabis, Placebo
Keywords: epilepsy, drug resistant, refractory, seizures, cannabidiol, cbd, cannabis
Medical subject headings: Drug Resistant Epilepsy, Epilepsy, Seizures, Color Vision Defects, Marijuana Abuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Medical CannabisDrug
Also called CBD/THC
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.
PlaceboDrug
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.

Study groups in NCT03808935
Study group	Role	What they receive
Medical cannabis	Experimental	Capsules containing cannabis extract, dissolved in high-oleic sunflower oil, and CBD/THC in a 16:1 ratio. Receives: 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Frequency of convulsive seizures
Measured: 0 - 10 weeks

Secondary outcomes (16)

Number of participants with treatment-related adverse events as assessed by the adverse events questionnaire
Measured: 0- 10 weeks
Changes in blood levels of CBD and THC from baseline to end of treatment
Measured: 0 - 10 weeks
Changes in blood levels of AEDs from baseline to end of treatment
Measured: 0 - 10 weeks
Changes in blood levels of liver enzymes AST, ALT, and GGT from baseline to end of treatment
Measured: 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
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.
Measured: 0 - 10 weeks
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
WHOQOL-BREF is a 26-item measure of physical health, psychological health, social relationships, and environment.
Measured: 0 - 10 weeks
Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life Childhood Epilepsy (QOLCE) questionnaire
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.
Measured: 0 - 10 weeks
Changes in symptoms of depression from baseline to end of treatment as assessed by the Neurological Disorder Depression Inventory for Epilepsy (NDDI-E)
NDDI-E is a 6-item questionnaire designed to screen for depression in adults with epilepsy.
Measured: 0 - 10 weeks
Changes in symptoms of depression from baseline to end of treatment as assessed by the Quick Inventory of Depressive Symptoms (QIDS)
QIDS is a 16-item measure designed to assess the severity of depressive symptoms.
Measured: 0 - 10 weeks
Changes in symptoms of anxiety from baseline to end of treatment as assessed by the Generalized Anxiety Disorder 7-item (GAD-7)
GAD-7 is a 7-item questionnaire assessing severity of generalized anxiety disorder.
Measured: 0 - 10 weeks
Change in overall severity of epilepsy from baseline to end of treatment as assessed by the Global Analysis of Severity of Epilepsy Scale (GASE)
GASE is a single-item, 7-point global rating scale that was designed to assess the overall severity of epilepsy.
Measured: 0 - 10 weeks
Change in quality of sleep from baseline to end of treatment as assessed by the Pittsburgh Sleep Quality Index (PSQI)
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.
Measured: 0 - 10 weeks
Change in participant's impression of change from baseline to end of treatment as assessed by the Patients' Global Impression of Change (PGIC) scale
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".
Measured: 0 - 10 weeks
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
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".
Measured: 0 - 10 weeks
Changes in psychological symptoms from baseline to end of treatment as assessed by the Brief Symptom Inventory (BSI-53)
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.
Measured: 0 - 10 weeks
Changes in functional impairment from baseline to end of treatment as assessed by the Sheehan Disability Scale (SDS)
SDS is a 5-item measure assessing functional impairment in three inter-related domains: work/school, social, and family life.
Measured: 0 - 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jan 201915 Mar 2020

First posted18 Jan 2019
Study start10 Jan 2019
Primary completion15 Mar 2020
Study completion15 Mar 2020

Why it stopped: Participants are no longer being examined or receiving intervention.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Drug Resistant EpilepsyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03808935
Sponsor's protocol ID: EPL29
Acronym: CERES
Status last verified: Sep 2020
First submitted: 11 Jan 2019
Last updated: 11 Sep 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With Tuberous Sclerosis Complex
Tuberous Sclerosis Complex
Not yet recruitingObservational study
Prospective Longitudinal Study of Sleep, Brain Activity, and Plasma Analyses in Patients Undergoing Epilepsy Surgery
Epilepsy, Sleep
Recruiting
Sleep-Sensitive Seizure Risk Assessment With Wearable EEGs
Epilepsy Intractable
RecruitingEarly Phase 1
Optimization of Deep Brain Stimulation Parameters in Patients With Medically Refractory Epilepsy
Refractory Epilepsy, Deep Brain Stimulation
Recruiting
Focused Ultrasound for Drug-resistant Epilepsy
Focused Ultrasound, MR-guided FUS

All Drug Resistant Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03808935
Acronym / sponsor ID: CERES / EPL29
Conditions: Drug Resistant Epilepsy
Keywords: epilepsy, drug resistant, refractory, seizures, cannabidiol, cbd, cannabis
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Participants are no longer being examined or receiving intervention.
Enrolment: 17 participants (actual)
Lead sponsor: The Epilepsy Research Program of the Ontario Brain InstituteUniversity, hospital or other
Collaborators: Ontario Brain Institute, University of Toronto, University Health Network, Toronto, London Health Sciences Centre, MedReleaf
Study start: 10 Jan 2019 (actual)
Primary completion: 15 Mar 2020 (actual)
Study completion: 15 Mar 2020 (actual)
First posted: 18 Jan 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Medical cannabis	Experimental	Drug: Medical CannabisCapsules containing cannabis extract, dissolved in high-oleic sunflower oil, and CBD/THC in a 16:1 ratio.
Placebo Control	Placebo comparator	Drug: PlaceboCapsules 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (9 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Medical CannabisAlso: CBD/THCThe 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.	Drug	Medical cannabis
PlaceboThe 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.	Drug	Placebo Control

Primary outcome

Frequency of convulsive seizures
Time frame: 0 - 10 weeks

16 secondary outcomes

Number of participants with treatment-related adverse events as assessed by the adverse events questionnaire
Time frame: 0- 10 weeks
Changes in blood levels of CBD and THC from baseline to end of treatment
Time frame: 0 - 10 weeks
Changes in blood levels of AEDs from baseline to end of treatment
Time frame: 0 - 10 weeks
Changes in blood levels of liver enzymes AST, ALT, and GGT from baseline to end of treatment
Time frame: 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
Time frame: 0 - 10 weeks
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
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
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
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
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
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
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
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
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
Changes in psychological symptoms from baseline to end of treatment as assessed by the Brief Symptom Inventory (BSI-53)
Time frame: 0 - 10 weeks
Changes in functional impairment from baseline to end of treatment as assessed by the Sheehan Disability Scale (SDS)
Time frame: 0 - 10 weeks

Results and safety

The study was stopped early (reason given: Participants are no longer being examined or receiving intervention.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2020.

Related trials for Drug Resistant Epilepsy

RecruitingPhase 3
Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With Tuberous Sclerosis Complex
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Prospective Longitudinal Study of Sleep, Brain Activity, and Plasma Analyses in Patients Undergoing Epilepsy Surgery
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

W M Burnham, PhD principal investigator

University of Toronto

Peter Tai, MD principal investigator

University Health Network, Toronto

Seyed Mirsattari, MD principal investigator

London Health Sciences Centre

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Medical Cannabis in people with Drug Resistant Epilepsy, run by The Epilepsy Research Program of the Ontario Brain Institute at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Participants are no longer being examined or receiving intervention.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of convulsive seizures (time frame: 0 - 10 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03808935.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2020; AzTrials last refreshed its copy on 27 Oct 2026.