Epileptic EncephalopathyPhase 1CARE-ENCT03024827
Cannabidiol in Children With Refractory Epileptic Encephalopathy
A Phase 1 study testing CanniMed® 1:20 in people with Epileptic Encephalopathy, run by University of Saskatchewan at 4 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 10 years
- Conditions the study is for
- Epileptic Encephalopathy
- What is being tested?
- CanniMed® 1:20
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesCanada
- Study dates
- 26 Apr 2017to 31 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Universite de Montreal
Montreal, Quebec, H3T1J4
University of Saskatchewan
Saskatoon, Saskatchewan, S7N5C5
University of British Columbia
Vancouver, British Columbia, V6T1Z4
University of Manitoba
Winnipeg, Manitoba, R3T 2N2
About this study
Official title: Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)
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.
Read the 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.
- Conditions
- Epileptic Encephalopathy
- Being tested
- CanniMed® 1:20
- 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)
- Medical subject headings
- Spasms, Infantile, Lennox Gastaut Syndrome, Epilepsies, Myoclonic, Landau-Kleffner Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanniMed® 1:20Drug
Also called Medical Cannabis Oil
A cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension.
| Study group | Role | What they receive |
|---|---|---|
| Medical Cannabis Oil | Experimental | CanniMed® 1:20 Receives: Drug: CanniMed® 1:20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Rate
Measured: Up to 6 months
Blood Pressure
Measured: Up to 6 months
Weight
Measured: Up to 6 months
Complete Blood Count (CBC) and Differential
Measured: Up to 6 months
Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)
Measured: Up to 6 months
Blood Urea Nitrogen (mmol/L)
Measured: Up to 6 months
Creatinine (umol/L)
Measured: Up to 6 months
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)
Measured: Up to 6 months
Total and Direct Bilirubin (umol/L)
Measured: Up to 6 months
Albumin (g/L)
Measured: Up to 6 months
Total Cholesterol and Triglyceride (mmol/L)
Measured: Up to 6 months
Clobazam and Norclobazam Levels (umol/L)
For participants taking clobazam who become excessively sedated
Measured: Up to 6 months
Clonazepam Level (umol/L)
For participants taking clonazepam who become excessively sedated
Measured: Up to 6 months
Urine Ketones
For participants on the ketogenic diet
Measured: Up to 6 months
Trough Level of Concomitant Anti-Convulsants
Measure interactions with any anti-convulsants participants may be already on
Measured: Up to 7 months
Adverse Events
Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea
Measured: Through study completion, up to 7 months
2-hour Electroencephalogram (EEG) Recording
Measured: Up to 6 months
Secondary outcomes (5)
Seizure Frequency Log Book
Measured: Through study completion, up to 7 months
Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)
Measured: Through study completion, up to 7 months
Cannabidiol (CBD) (ng/mL)
Levels in blood
Measured: Up to 7 months
Tetrahydrocannabinol (Δ9-THC) (ng/mL)
Levels in blood
Measured: Up to 7 months
11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)
Levels in blood
Measured: Up to 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2017 (estimated)
- Study start26 Apr 2017
- Primary completion1 Feb 2020
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Epileptic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Saskatchewan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Huntsman, University of Saskatchewan
- Investigators
- Richard Huntsman, MD, Principal investigator, Dalhousie UniversityRichard Tang-Wai, MD, Principal investigator, Loma Linda UniversityJane Alcorn, PhD, Principal investigator, University of Saskatchewan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03024827
- Sponsor's protocol ID
- CARE-E-01
- Acronym
- CARE-E
- Status last verified
- Apr 2023
- First submitted
- 16 Dec 2016
- Last updated
- 26 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 29981580Huntsman 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.
PubMed 31333569
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)
- ClinicalTrials.gov ID
- NCT03024827
- Acronym / sponsor ID
- CARE-E / CARE-E-01
- 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)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of SaskatchewanUniversity, hospital or other
- Study start
- 26 Apr 2017 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 19 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Medical Cannabis Oil | Experimental | Drug: CanniMed® 1:20CanniMed® 1:20 |
Who may qualify
- Ages
- 1 year to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanniMed® 1:20Also: Medical Cannabis OilA cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension. | Drug | Medical Cannabis Oil |
Primary outcome
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
5 secondary outcomes
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
Tetrahydrocannabinol (Δ9-THC) (ng/mL)
Time frame: Up to 7 months
11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)
Time frame: Up to 7 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2023.
- Background: PubMed 29981580Reithmeier 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 publication: PubMed 31333569Huntsman 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.
- Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E StudyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Huntsman, MD principal investigator
Dalhousie University
Richard Tang-Wai, MD principal investigator
Loma Linda University
Jane Alcorn, PhD principal investigator
University of Saskatchewan
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CanniMed® 1:20 in people with Epileptic Encephalopathy, run by University of Saskatchewan at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart Rate (time frame: Up to 6 months). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03024827, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2023.