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

• ClinicalTrials.gov Identifier: NCT03024827
• Recruitment Status: Active, not recruiting
• First Posted: January 19, 2017
• Last Update Posted: September 28, 2021
• Sponsor: University of Saskatchewan
• Information provided by (Responsible Party): Richard Huntsman, University of Saskatchewan

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Epileptic Encephalopathy	Drug: CanniMed® 1:20	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)
• Actual Study Start Date: April 26, 2017
• Actual Primary Completion Date: February 1, 2020
• Estimated Study Completion Date: January 1, 2022

Arms and Interventions

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 Name: Medical Cannabis Oil

Outcome Measures

Primary Outcome Measures :

1. Heart Rate [ Time Frame: Up to 6 months ]
2. Blood Pressure [ Time Frame: Up to 6 months ]
3. Weight [ Time Frame: Up to 6 months ]
4. Complete Blood Count (CBC) and Differential [ Time Frame: Up to 6 months ]
5. Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L) [ Time Frame: Up to 6 months ]
6. Blood Urea Nitrogen (mmol/L) [ Time Frame: Up to 6 months ]
7. Creatinine (umol/L) [ Time Frame: Up to 6 months ]
8. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L) [ Time Frame: Up to 6 months ]
9. Total and Direct Bilirubin (umol/L) [ Time Frame: Up to 6 months ]
10. Albumin (g/L) [ Time Frame: Up to 6 months ]
11. Total Cholesterol and Triglyceride (mmol/L) [ Time Frame: Up to 6 months ]
12. Clobazam and Norclobazam Levels (umol/L) [ Time Frame: Up to 6 months ]
    For participants taking clobazam who become excessively sedated
13. Clonazepam Level (umol/L) [ Time Frame: Up to 6 months ]
    For participants taking clonazepam who become excessively sedated
14. Urine Ketones [ Time Frame: Up to 6 months ]
    For participants on the ketogenic diet
15. Trough Level of Concomitant Anti-Convulsants [ Time Frame: Up to 7 months ]
    Measure interactions with any anti-convulsants participants may be already on
16. Adverse Events [ Time Frame: Through study completion, up to 7 months ]
    Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea
17. 2-hour Electroencephalogram (EEG) Recording [ Time Frame: Up to 6 months ]

Secondary Outcome Measures :

1. Seizure Frequency Log Book [ Time Frame: Through study completion, up to 7 months ]
2. Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE) [ Time Frame: Through study completion, up to 7 months ]
3. Cannabidiol (CBD) (ng/mL) [ Time Frame: Up to 7 months ]
   Levels in blood
4. Tetrahydrocannabinol (Δ9-THC) (ng/mL) [ Time Frame: Up to 7 months ]
   Levels in blood
5. 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL) [ Time Frame: Up to 7 months ]
   Levels in blood

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 10 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Canada, British Columbia

University of British Columbia

Vancouver, British Columbia, Canada, V6T1Z4

Canada, Manitoba

University of Manitoba

Winnipeg, Manitoba, Canada, R3T 2N2

Canada, Quebec

Universite de Montreal

Montreal, Quebec, Canada, H3T1J4

Canada, Saskatchewan

University of Saskatchewan

Saskatoon, Saskatchewan, Canada, S7N5C5

Sponsors and Collaborators

University of Saskatchewan

Investigators

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

More Information

Additional Information:

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

Publications of Results:

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.

Other 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.

• Responsible Party: Richard Huntsman, MD, University of Saskatchewan
• ClinicalTrials.gov Identifier: NCT03024827
• Other Study ID Numbers: CARE-E-01
• First Posted: January 19, 2017
• Last Update Posted: September 28, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Richard Huntsman, University of Saskatchewan:

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:

Brain Diseases; Epilepsy; Central Nervous System Diseases; Nervous System Diseases