Cannabidiol in Children With Refractory Epileptic Encephalopathy

Epileptic Encephalopathy Clinical Trial

— CARE-E  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03024827
• Other study ID #: CARE-E-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 26, 2017
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2023
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 10 Years

Eligibility

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)

Related Conditions & MeSH terms

• Brain Diseases
• Epilepsy
• Epileptic Encephalopathy

Intervention

Drug:
• CanniMed® 1:20
A cannabidiol (CBD): tetrahydrocannabinol (?9 THC) 20:1 ratio product will be provided as an oil-based suspension.

Locations

Country	Name	City	State
Canada	Universite de Montreal	Montreal	Quebec
Canada	University of Saskatchewan	Saskatoon	Saskatchewan
Canada	University of British Columbia	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Saskatchewan

Country where clinical trial is conducted

Canada, 

References & Publications (2)

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 Childr — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart Rate		Up to 6 months
Primary	Blood Pressure		Up to 6 months
Primary	Weight		Up to 6 months
Primary	Complete Blood Count (CBC) and Differential		Up to 6 months
Primary	Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)		Up to 6 months
Primary	Blood Urea Nitrogen (mmol/L)		Up to 6 months
Primary	Creatinine (umol/L)		Up to 6 months
Primary	Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)		Up to 6 months
Primary	Total and Direct Bilirubin (umol/L)		Up to 6 months
Primary	Albumin (g/L)		Up to 6 months
Primary	Total Cholesterol and Triglyceride (mmol/L)		Up to 6 months
Primary	Clobazam and Norclobazam Levels (umol/L)	For participants taking clobazam who become excessively sedated	Up to 6 months
Primary	Clonazepam Level (umol/L)	For participants taking clonazepam who become excessively sedated	Up to 6 months
Primary	Urine Ketones	For participants on the ketogenic diet	Up to 6 months
Primary	Trough Level of Concomitant Anti-Convulsants	Measure interactions with any anti-convulsants participants may be already on	Up to 7 months
Primary	Adverse Events	Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea	Through study completion, up to 7 months
Primary	2-hour Electroencephalogram (EEG) Recording		Up to 6 months
Secondary	Seizure Frequency Log Book		Through study completion, up to 7 months
Secondary	Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)		Through study completion, up to 7 months
Secondary	Cannabidiol (CBD) (ng/mL)	Levels in blood	Up to 7 months
Secondary	Tetrahydrocannabinol (?9-THC) (ng/mL)	Levels in blood	Up to 7 months
Secondary	11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)	Levels in blood	Up to 7 months

External Links

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