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: October 17, 2019
• Sponsor: University of Saskatchewan
• Information provided by (Responsible Party): Richard Huntsman, University of Saskatchewan

Tracking Information

• First Submitted Date: December 16, 2016
• First Posted Date: January 19, 2017
• Last Update Posted Date: October 17, 2019
• Actual Study Start Date: April 26, 2017
• Estimated Primary Completion Date: February 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2018)

• Heart Rate [ Time Frame: Up to 6 months ]
• Blood Pressure [ Time Frame: Up to 6 months ]
• Weight [ Time Frame: Up to 6 months ]
• Complete Blood Count (CBC) and Differential [ Time Frame: Up to 6 months ]
• Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L) [ Time Frame: Up to 6 months ]
• Blood Urea Nitrogen (mmol/L) [ Time Frame: Up to 6 months ]
• Creatinine (umol/L) [ Time Frame: Up to 6 months ]
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L) [ Time Frame: Up to 6 months ]
• Total and Direct Bilirubin (umol/L) [ Time Frame: Up to 6 months ]
• Albumin (g/L) [ Time Frame: Up to 6 months ]
• Total Cholesterol and Triglyceride (mmol/L) [ Time Frame: Up to 6 months ]
• Clobazam and Norclobazam Levels (umol/L) [ Time Frame: Up to 6 months ]
  For participants taking clobazam who become excessively sedated
• Clonazepam Level (umol/L) [ Time Frame: Up to 6 months ]
  For participants taking clonazepam who become excessively sedated
• Urine Ketones [ Time Frame: Up to 6 months ]
  For participants on the ketogenic diet
• Trough Level of Concomitant Anti-Convulsants [ Time Frame: Up to 7 months ]
  Measure interactions with any anti-convulsants participants may be already on
• 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
• 2-hour Electroencephalogram (EEG) Recording [ Time Frame: Up to 6 months ]

Original Primary Outcome Measures (submitted: January 18, 2017)

• Heart Rate [ Time Frame: Up to 6 months ]
• Blood Pressure [ Time Frame: Up to 6 months ]
• Weight [ Time Frame: Up to 6 months ]
• Complete Blood Count (CBC) and Differential [ Time Frame: Up to 6 months ]
• Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L) [ Time Frame: Up to 6 months ]
• Blood Urea Nitrogen (mmol/L) [ Time Frame: Up to 6 months ]
• Creatinine (umol/L) [ Time Frame: Up to 6 months ]
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L) [ Time Frame: Up to 6 months ]
• Total and Direct Bilirubin (umol/L) [ Time Frame: Up to 6 months ]
• Albumin (g/L) [ Time Frame: Up to 6 months ]
• Total Cholesterol and Triglyceride (mmol/L) [ Time Frame: Up to 6 months ]
• Clobazam and Norclobazam Levels (umol/L) [ Time Frame: Up to 6 months ]
  For participants taking clobazam who become excessively sedated
• Urine Ketones [ Time Frame: Up to 6 months ]
  For participants on the ketogenic diet
• Trough Level of Concomitant Anti-Convulsants [ Time Frame: Up to 6 months ]
  Measure interactions with any anti-convulsants participants may be already on
• 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
• 2-hour Electroencephalogram (EEG) Recording [ Time Frame: Up to 6 months ]

Current Secondary Outcome Measures (submitted: October 10, 2018)

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

Original Secondary Outcome Measures (submitted: January 18, 2017)

• Seizure Frequency Log Book [ Time Frame: Through study completion, up to 7 months ]
• Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE) [ Time Frame: Through study completion, up to 7 months ]
• Cannabidiol (CBD) (ng/mL) [ Time Frame: Up to 6 months ]
  Levels in blood
• Tetrahydrocannabinol (Δ9-THC) (ng/mL) [ Time Frame: Up to 6 months ]
  Levels in blood
• 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL) [ Time Frame: Up to 6 months ]
  Levels in blood

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epileptic Encephalopathy

Intervention

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

Study Arms

Experimental: Medical Cannabis Oil

CanniMed® 1:20

Intervention: Drug: CanniMed® 1:20

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 15, 2019): 20
• Original Estimated Enrollment (submitted: January 18, 2017): 30
• Estimated Study Completion Date: September 1, 2020
• Estimated Primary Completion Date: February 1, 2020 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 10 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT03024827
• Other Study ID Numbers: CARE-E-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Richard Huntsman, University of Saskatchewan
• Study Sponsor: University of Saskatchewan
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Saskatchewan
• Verification Date: October 2019