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

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ClinicalTrials.gov Identifier: NCT03024827
Recruitment Status : Recruiting
First Posted : January 19, 2017
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
Richard Huntsman, University of Saskatchewan

Tracking Information
First Submitted Date  ICMJE December 16, 2016
First Posted Date  ICMJE January 19, 2017
Last Update Posted Date October 15, 2018
Actual Study Start Date  ICMJE April 26, 2017
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History Complete list of historical versions of study NCT03024827 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Cannabidiol in Children With Refractory Epileptic Encephalopathy
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epileptic Encephalopathy
Intervention  ICMJE 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  ICMJE 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 10, 2018)		 28
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2017)		 30
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 10 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Doris Newmeyer 306-844-1208 doris.newmeyer@usask.ca
Contact: Simona Meier 306-978-8302 simona.meier@usask.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03024827
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Richard Huntsman, University of Saskatchewan
Study Sponsor  ICMJE University of Saskatchewan
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP