MedPath

Cannabidiol in Children With Refractory Epileptic Encephalopathy

Phase 1
Active, not recruiting
Conditions
Epileptic Encephalopathy
Registration Number
NCT03024827
Lead Sponsor
University of Saskatchewan
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
20
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Total Cholesterol and Triglyceride (mmol/L)Up to 6 months
Clobazam and Norclobazam Levels (umol/L)Up to 6 months

For participants taking clobazam who become excessively sedated

Clonazepam Level (umol/L)Up to 6 months

For participants taking clonazepam who become excessively sedated

Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/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
WeightUp to 6 months
Blood Urea Nitrogen (mmol/L)Up to 6 months
Trough Level of Concomitant Anti-ConvulsantsUp to 7 months

Measure interactions with any anti-convulsants participants may be already on

2-hour Electroencephalogram (EEG) RecordingUp to 6 months
Complete Blood Count (CBC) and DifferentialUp to 6 months
Urine KetonesUp to 6 months

For participants on the ketogenic diet

Adverse EventsThrough study completion, up to 7 months

Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea

Heart RateUp to 6 months
Creatinine (umol/L)Up to 6 months
Total and Direct Bilirubin (umol/L)Up to 6 months
Albumin (g/L)Up to 6 months
Blood PressureUp to 6 months
Secondary Outcome Measures
NameTimeMethod
11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)Up to 7 months

Levels in blood

Seizure Frequency Log BookThrough study completion, up to 7 months
Cannabidiol (CBD) (ng/mL)Up to 7 months

Levels in blood

Tetrahydrocannabinol (Δ9-THC) (ng/mL)Up to 7 months

Levels in blood

Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)Through study completion, up to 7 months

Trial Locations

Locations (4)

University of British Columbia

🇨🇦

Vancouver, British Columbia, Canada

University of Saskatchewan

🇨🇦

Saskatoon, Saskatchewan, Canada

Universite de Montreal

🇨🇦

Montreal, Quebec, Canada

University of Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

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