Back to resultsCannabidiol in Children With Refractory Epileptic Encephalopathy (CARE-E)
Primary Purpose
Epileptic Encephalopathy
Status
Active
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
CanniMed® 1:20
Sponsored by
About this trial
This is an interventional treatment trial for Epileptic Encephalopathy focused on measuring Infantile Spasms, Lennox Gastaut Syndrome, Doose Syndrome, Continuous Spike Wave in Sleep, Landau-Kleffner Syndrome, Dravet Syndrome, Malignant Migrating Partial Seizures of Infancy (MMPSI)
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)
Sites / Locations
- University of British Columbia
- University of Manitoba
- Universite de Montreal
- University of Saskatchewan
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Medical Cannabis Oil
Arm Description
CanniMed® 1:20
Outcomes
Primary Outcome Measures
Heart Rate
Blood Pressure
Weight
Complete Blood Count (CBC) and Differential
Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)
Blood Urea Nitrogen (mmol/L)
Creatinine (umol/L)
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)
Total and Direct Bilirubin (umol/L)
Albumin (g/L)
Total Cholesterol and Triglyceride (mmol/L)
Clobazam and Norclobazam Levels (umol/L)
For participants taking clobazam who become excessively sedated
Clonazepam Level (umol/L)
For participants taking clonazepam who become excessively sedated
Urine Ketones
For participants on the ketogenic diet
Trough Level of Concomitant Anti-Convulsants
Measure interactions with any anti-convulsants participants may be already on
Adverse Events
Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea
2-hour Electroencephalogram (EEG) Recording
Secondary Outcome Measures
Seizure Frequency Log Book
Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)
Cannabidiol (CBD) (ng/mL)
Levels in blood
Tetrahydrocannabinol (Δ9-THC) (ng/mL)
Levels in blood
11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)
Levels in blood
Full Information
NCT ID
NCT03024827
First Posted
December 16, 2016
Last Updated
April 24, 2023
Sponsor
University of Saskatchewan
1. Study Identification
Unique Protocol Identification Number
NCT03024827
Brief Title
Cannabidiol in Children With Refractory Epileptic Encephalopathy
Acronym
CARE-E
Official Title
Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 26, 2017 (Actual)
Primary Completion Date
February 1, 2020 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Saskatchewan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Medical Cannabis Oil
Arm Type
Experimental
Arm Description
CanniMed® 1:20
Intervention Type
Drug
Intervention Name(s)
CanniMed® 1:20
Other Intervention Name(s)
Medical Cannabis Oil
Intervention Description
A cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension.
Primary Outcome Measure Information:
Title
Heart Rate
Time Frame
Up to 6 months
Title
Blood Pressure
Time Frame
Up to 6 months
Title
Weight
Time Frame
Up to 6 months
Title
Complete Blood Count (CBC) and Differential
Time Frame
Up to 6 months
Title
Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)
Time Frame
Up to 6 months
Title
Blood Urea Nitrogen (mmol/L)
Time Frame
Up to 6 months
Title
Creatinine (umol/L)
Time Frame
Up to 6 months
Title
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)
Time Frame
Up to 6 months
Title
Total and Direct Bilirubin (umol/L)
Time Frame
Up to 6 months
Title
Albumin (g/L)
Time Frame
Up to 6 months
Title
Total Cholesterol and Triglyceride (mmol/L)
Time Frame
Up to 6 months
Title
Clobazam and Norclobazam Levels (umol/L)
Description
For participants taking clobazam who become excessively sedated
Time Frame
Up to 6 months
Title
Clonazepam Level (umol/L)
Description
For participants taking clonazepam who become excessively sedated
Time Frame
Up to 6 months
Title
Urine Ketones
Description
For participants on the ketogenic diet
Time Frame
Up to 6 months
Title
Trough Level of Concomitant Anti-Convulsants
Description
Measure interactions with any anti-convulsants participants may be already on
Time Frame
Up to 7 months
Title
Adverse Events
Description
Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea
Time Frame
Through study completion, up to 7 months
Title
2-hour Electroencephalogram (EEG) Recording
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Seizure Frequency Log Book
Time Frame
Through study completion, up to 7 months
Title
Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)
Time Frame
Through study completion, up to 7 months
Title
Cannabidiol (CBD) (ng/mL)
Description
Levels in blood
Time Frame
Up to 7 months
Title
Tetrahydrocannabinol (Δ9-THC) (ng/mL)
Description
Levels in blood
Time Frame
Up to 7 months
Title
11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)
Description
Levels in blood
Time Frame
Up to 7 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Huntsman, MD
Organizational Affiliation
Dalhousie University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard Tang-Wai, MD
Organizational Affiliation
Loma Linda University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jane Alcorn, PhD
Organizational Affiliation
University of Saskatchewan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T1Z4
Country
Canada
Facility Name
University of Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3T 2N2
Country
Canada
Facility Name
Universite de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T1J4
Country
Canada
Facility Name
University of Saskatchewan
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N5C5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29981580
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.
Results Reference
background
PubMed Identifier
31333569
Citation
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.
Results Reference
result
Links:
URL
https://www.frontiersin.org/articles/10.3389/fneur.2019.00716/full
Description
Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study
Learn more about this trial
Cannabidiol in Children With Refractory Epileptic Encephalopathy
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