Cannabidiol in Children With Refractory Epileptic Encephalopathy

Study Overview
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Brief Summary
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This study will assess the safety and tolerability of a cannabidiol-enriched Cannabis Herbal Extract in a small group of children with refractory epileptic encephalopathy. The dosage of Cannabis Herbal Extract will be gradually increased over a four month time period.

Detailed Description
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Epileptic Encephalopathies are a group of epilepsies that develop in children. These epilepsies can cause frequent and difficult to control seizures. Because of the ongoing seizures, these epilepsies can also cause cognitive impairment and neurological impairment. In many children with these Epileptic Encephalopathies, seizures are difficult to control with medical treatment, such as anti-convulsants or non-drug treatments like the ketogenic diet (a high fat, adequate-protein, low-carbohydrate diet). This has resulted in a need to find therapies that are effective and better tolerated for children with epileptic encephalopathies. There is very limited data regarding the use of cannabis products in children, in particular cannabidiol-enriched cannabis oil in children with epilepsy. However, hemp oil products with high cannabidiol and low tetrahydrocannabinol ratios have been reported to provide seizure relief and cognitive improvement in children who take them.

Official Title
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Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)

Conditions
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Epileptic Encephalopathy

Intervention / Treatment
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* Drug: CanniMed® 1:20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 1-10 years Epileptic Encephalopathy A minimum of at least 1 major seizure per week or 4 major seizures per month. For the purposes of this research study, a major seizure would include atonic, tonic, clonic, tonic-clonic, major myoclonic, myoclonic astatic seizures and epileptic spasms (including infantile spasms) Refractory to anticonvulsant medication as per the International League Against Epilepsy (ILAE) Definition of failing 2 appropriate anticonvulsants at therapeutic doses The ability to attend appointments regularly Negative pregnancy test at screening for females who have reached menarche Exclusion Criteria: Recent (<1 month) change in anticonvulsant therapies including anticonvulsant medications, ketogenic diet or settings on Vagal Nerve Stimulator Recent (<6 months) change in intravenous immunoglobulin (IVIG) treatment Initiation of ketogenic diet within 6 months (Patients must be on the ketogenic diet for at least 6 months to prevent any delayed response from the ketogenic diet affecting study results) Implantation and activation of Vagal Nerve Stimulator within 12 months (Patients may have a vagal nerve stimulator for at least one year once again to prevent delayed response from the vagal nerve stimulator affecting study results) Use of cannabis-based therapy within 2 months (Participants who have previously used a cannabis based therapy may be included if they have a 2 month period without use of cannabis based therapy prior to enrolment in the study) Use of selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant or atypical neuroleptic medication in last month Concomitant regular use of narcotics (Use of narcotics in emergency situations and supervised by a physician is allowed) Initiation or dosage change of oral or injected steroids within 3 months Allergy or known intolerance to any of the compounds within the study preparation Inability of study participants to attend assessments on a monthly basis Clinically significant cardiac, renal or hepatic disease (as assessed by the site investigator)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medical Cannabis Oil<br>CanniMed® 1:20 | Drug: CanniMed® 1:20<br>* A cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension.<br>* Other names: Medical Cannabis Oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate |  | Up to 6 months | 
| Blood Pressure |  | Up to 6 months | 
| Weight |  | Up to 6 months | 
| Complete Blood Count (CBC) and Differential |  | Up to 6 months | 
| Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L) |  | Up to 6 months | 
| Blood Urea Nitrogen (mmol/L) |  | Up to 6 months | 
| Creatinine (umol/L) |  | Up to 6 months | 
| Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L) |  | Up to 6 months | 
| Total and Direct Bilirubin (umol/L) |  | Up to 6 months | 
| Albumin (g/L) |  | Up to 6 months | 
| Total Cholesterol and Triglyceride (mmol/L) |  | Up to 6 months | 
| Clobazam and Norclobazam Levels (umol/L) | For participants taking clobazam who become excessively sedated | Up to 6 months | 
| Clonazepam Level (umol/L) | For participants taking clonazepam who become excessively sedated | Up to 6 months | 
| Urine Ketones | For participants on the ketogenic diet | Up to 6 months | 
| Trough Level of Concomitant Anti-Convulsants | Measure interactions with any anti-convulsants participants may be already on | Up to 7 months | 
| Adverse Events | Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea | Through study completion, up to 7 months | 
| 2-hour Electroencephalogram (EEG) Recording |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure Frequency Log Book |  | Through study completion, up to 7 months | 
| Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE) |  | Through study completion, up to 7 months | 
| Cannabidiol (CBD) (ng/mL) | Levels in blood | Up to 7 months | 
| Tetrahydrocannabinol (Δ9-THC) (ng/mL) | Levels in blood | Up to 7 months | 
| 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL) | Levels in blood | Up to 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infantile Spasms, Lennox Gastaut Syndrome, Doose Syndrome, Continuous Spike Wave in Sleep, Landau-Kleffner Syndrome, Dravet Syndrome, Malignant Migrating Partial Seizures of Infancy (MMPSI)