Cannabidiol in Children With Refractory Epileptic Encephalopathy (CARE-E)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Epileptic Encephalopathy
• Intervention / Treatment: Drug: CanniMed® 1:20

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T1Z4
      • University of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3T 2N2
      • University of Manitoba
  • Quebec
    • Montreal, Quebec, Canada, H3T1J4
      • Université de Montréal
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N5C5
      • University of Saskatchewan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Richard Tang-Wai, MD, Loma Linda University; Principal Investigator: Richard Huntsman, MD, Dalhousie University

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2017
• Primary Completion (Actual): February 1, 2020
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 16, 2016
• First Submitted That Met QC Criteria: January 18, 2017
• First Posted (Estimate): January 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Brain Diseases
• Other Study ID Numbers: CARE-E-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No