Cannabidiol in Children With Refractory Epileptic Encephalopathy

NCT03024827 | Unknown Phase 1

• 1 other identifier: CARE-E-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

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.

Conditions

Epileptic Encephalopathy

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)

Outcome Measures

Primary Outcomes (17)

• 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 Outcomes (5)

• 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)

  Up to 7 months

• Tetrahydrocannabinol (Δ9-THC) (ng/mL)

  Up to 7 months

• 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)

  Up to 7 months

Study Arms (1)

Medical Cannabis Oil

EXPERIMENTAL

CanniMed® 1:20

Drug: CanniMed® 1:20

Interventions

CanniMed® 1:20 DRUG

A cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension.

Also known as: Medical Cannabis Oil

Medical Cannabis Oil

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Saskatchewan: lead

Study Sites (4)

University of British Columbia

Vancouver, British Columbia, V6T1Z4, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3T 2N2, Canada

Location

Universite de Montreal

Montreal, Quebec, H3T1J4, Canada

Location

University of Saskatchewan

Saskatoon, Saskatchewan, S7N5C5, Canada

Location

Related Publications (2)

• 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.

  PMID: 29981580 BACKGROUND

• 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.

  PMID: 31333569 RESULT

Related Links

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

MeSH Terms

Conditions

Spasms, Infantile; Lennox Gastaut Syndrome; Epilepsies, Myoclonic; Landau-Kleffner Syndrome

Interventions

Medical Marijuana

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Richard Huntsman, MD

  Dalhousie University

  PRINCIPAL INVESTIGATOR

• Richard Tang-Wai, MD

  Loma Linda University

  PRINCIPAL INVESTIGATOR

• Jane Alcorn, PhD

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: January 19, 2017
• Study Start: April 26, 2017
• Primary Completion: February 1, 2020
• Study Completion: December 31, 2023
• Last Updated: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)