Clinical trial NCT03024827: Cannabidiol in Children With Refractory Epileptic Encephalopathy
Official title: Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Epileptic Encephalopathy
Keywords: Infantile Spasms
Lennox Gastaut Syndrome
Doose Syndrome
Continuous Spike Wave in Sleep
Landau-Kleffner Syndrome
Dravet Syndrome
Malignant Migrating Partial Seizures of Infancy (MMPSI)
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
First posted: 2017-01-19
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Heart Rate
timeFrame: Up to 6 months
measure: Blood Pressure
timeFrame: Up to 6 months
measure: Weight
timeFrame: Up to 6 months
measure: Complete Blood Count (CBC) and Differential
timeFrame: Up to 6 months
measure: Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)
timeFrame: Up to 6 months
measure: Blood Urea Nitrogen (mmol/L)
timeFrame: Up to 6 months
measure: Creatinine (umol/L)
timeFrame: Up to 6 months
measure: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)
timeFrame: Up to 6 months
measure: Total and Direct Bilirubin (umol/L)
timeFrame: Up to 6 months
measure: Albumin (g/L)
timeFrame: Up to 6 months
measure: Total Cholesterol and Triglyceride (mmol/L)
timeFrame: Up to 6 months
measure: Clobazam and Norclobazam Levels (umol/L)
timeFrame: Up to 6 months
measure: Clonazepam Level (umol/L)
timeFrame: Up to 6 months
measure: Urine Ketones
timeFrame: Up to 6 months
measure: Trough Level of Concomitant Anti-Convulsants
timeFrame: Up to 7 months
measure: Adverse Events
timeFrame: Through study completion, up to 7 months
measure: 2-hour Electroencephalogram (EEG) Recording
timeFrame: Up to 6 months
Secondary outcomes:
measure: Seizure Frequency Log Book
timeFrame: Through study completion, up to 7 months
measure: Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)
timeFrame: Through study completion, up to 7 months
measure: Cannabidiol (CBD) (ng/mL)
timeFrame: Up to 7 months
measure: Tetrahydrocannabinol (Δ9-THC) (ng/mL)
timeFrame: Up to 7 months
measure: 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)
timeFrame: Up to 7 months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Montreal
country: Canada
facility: Universite de Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: Dalhousie University
name: Richard Huntsman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loma Linda University
name: Richard Tang-Wai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Saskatchewan
name: Jane Alcorn, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reithmeier D, Tang-Wai R, Seifert B, Lyon AW, Alcorn J, Acton B, Corley S, Prosser-Loose E, Mousseau DD, Lim HJ, Tellez-Zenteno J, Huh L, Leung E, Carmant L, Huntsman RJ. The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study. BMC Pediatr. 2018 Jul 7;18(1):221. doi: 10.1186/s12887-018-1191-y.
citation: Huntsman RJ, Tang-Wai R, Alcorn J, Vuong S, Acton B, Corley S, Laprairie R, Lyon AW, Meier S, Mousseau DD, Newmeyer D, Prosser-Loose E, Seifert B, Tellez-Zenteno J, Huh L, Leung E, Major P. Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study. Front Neurol. 2019 Jul 3;10:716. doi: 10.3389/fneur.2019.00716. eCollection 2019.