<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03024827</url>
  </required_header>
  <id_info>
    <org_study_id>CARE-E-01</org_study_id>
    <nct_id>NCT03024827</nct_id>
  </id_info>
  <brief_title>Cannabidiol in Children With Refractory Epileptic Encephalopathy</brief_title>
  <acronym>CARE-E</acronym>
  <official_title>Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Saskatchewan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Saskatchewan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the safety and tolerability of a cannabidiol-enriched Cannabis Herbal&#xD;
      Extract in a small group of children with refractory epileptic encephalopathy. The dosage of&#xD;
      Cannabis Herbal Extract will be gradually increased over a four month time period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Epileptic Encephalopathies are a group of epilepsies that develop in children. These&#xD;
      epilepsies can cause frequent and difficult to control seizures. Because of the ongoing&#xD;
      seizures, these epilepsies can also cause cognitive impairment and neurological impairment.&#xD;
&#xD;
      In many children with these Epileptic Encephalopathies, seizures are difficult to control&#xD;
      with medical treatment, such as anti-convulsants or non-drug treatments like the ketogenic&#xD;
      diet (a high fat, adequate-protein, low-carbohydrate diet). This has resulted in a need to&#xD;
      find therapies that are effective and better tolerated for children with epileptic&#xD;
      encephalopathies.&#xD;
&#xD;
      There is very limited data regarding the use of cannabis products in children, in particular&#xD;
      cannabidiol-enriched cannabis oil in children with epilepsy. However, hemp oil products with&#xD;
      high cannabidiol and low tetrahydrocannabinol ratios have been reported to provide seizure&#xD;
      relief and cognitive improvement in children who take them.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 26, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">February 1, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood Pressure</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Weight</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Blood Count (CBC) and Differential</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood Urea Nitrogen (mmol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Creatinine (umol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total and Direct Bilirubin (umol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Albumin (g/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Cholesterol and Triglyceride (mmol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clobazam and Norclobazam Levels (umol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>For participants taking clobazam who become excessively sedated</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clonazepam Level (umol/L)</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>For participants taking clonazepam who become excessively sedated</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Ketones</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>For participants on the ketogenic diet</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough Level of Concomitant Anti-Convulsants</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Measure interactions with any anti-convulsants participants may be already on</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Through study completion, up to 7 months</time_frame>
    <description>Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2-hour Electroencephalogram (EEG) Recording</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seizure Frequency Log Book</measure>
    <time_frame>Through study completion, up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)</measure>
    <time_frame>Through study completion, up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cannabidiol (CBD) (ng/mL)</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Levels in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tetrahydrocannabinol (Δ9-THC) (ng/mL)</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Levels in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Levels in blood</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Epileptic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Medical Cannabis Oil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CanniMed® 1:20</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CanniMed® 1:20</intervention_name>
    <description>A cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension.</description>
    <arm_group_label>Medical Cannabis Oil</arm_group_label>
    <other_name>Medical Cannabis Oil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 1-10 years&#xD;
&#xD;
          -  Epileptic Encephalopathy&#xD;
&#xD;
          -  A minimum of at least 1 major seizure per week or 4 major seizures per month. For the&#xD;
             purposes of this research study, a major seizure would include atonic, tonic, clonic,&#xD;
             tonic-clonic, major myoclonic, myoclonic astatic seizures and epileptic spasms&#xD;
             (including infantile spasms)&#xD;
&#xD;
          -  Refractory to anticonvulsant medication as per the International League Against&#xD;
             Epilepsy (ILAE) Definition of failing 2 appropriate anticonvulsants at therapeutic&#xD;
             doses&#xD;
&#xD;
          -  The ability to attend appointments regularly&#xD;
&#xD;
          -  Negative pregnancy test at screening for females who have reached menarche&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recent (&lt;1 month) change in anticonvulsant therapies including anticonvulsant&#xD;
             medications, ketogenic diet or settings on Vagal Nerve Stimulator&#xD;
&#xD;
          -  Recent (&lt;6 months) change in intravenous immunoglobulin (IVIG) treatment&#xD;
&#xD;
          -  Initiation of ketogenic diet within 6 months (Patients must be on the ketogenic diet&#xD;
             for at least 6 months to prevent any delayed response from the ketogenic diet&#xD;
             affecting study results)&#xD;
&#xD;
          -  Implantation and activation of Vagal Nerve Stimulator within 12 months (Patients may&#xD;
             have a vagal nerve stimulator for at least one year once again to prevent delayed&#xD;
             response from the vagal nerve stimulator affecting study results)&#xD;
&#xD;
          -  Use of cannabis-based therapy within 2 months (Participants who have previously used a&#xD;
             cannabis based therapy may be included if they have a 2 month period without use of&#xD;
             cannabis based therapy prior to enrolment in the study)&#xD;
&#xD;
          -  Use of selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant or&#xD;
             atypical neuroleptic medication in last month&#xD;
&#xD;
          -  Concomitant regular use of narcotics (Use of narcotics in emergency situations and&#xD;
             supervised by a physician is allowed)&#xD;
&#xD;
          -  Initiation or dosage change of oral or injected steroids within 3 months&#xD;
&#xD;
          -  Allergy or known intolerance to any of the compounds within the study preparation&#xD;
&#xD;
          -  Inability of study participants to attend assessments on a monthly basis&#xD;
&#xD;
          -  Clinically significant cardiac, renal or hepatic disease (as assessed by the site&#xD;
             investigator)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>10 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Huntsman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dalhousie University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Richard Tang-Wai, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loma Linda University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jane Alcorn, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Saskatchewan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of British Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6T1Z4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3T 2N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T1J4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Saskatchewan</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7N5C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>https://www.frontiersin.org/articles/10.3389/fneur.2019.00716/full</url>
    <description>Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study</description>
  </link>
  <reference>
    <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.</citation>
    <PMID>29981580</PMID>
  </reference>
  <results_reference>
    <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.</citation>
    <PMID>31333569</PMID>
  </results_reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Saskatchewan</investigator_affiliation>
    <investigator_full_name>Richard Huntsman</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Infantile Spasms</keyword>
  <keyword>Lennox Gastaut Syndrome</keyword>
  <keyword>Doose Syndrome</keyword>
  <keyword>Continuous Spike Wave in Sleep</keyword>
  <keyword>Landau-Kleffner Syndrome</keyword>
  <keyword>Dravet Syndrome</keyword>
  <keyword>Malignant Migrating Partial Seizures of Infancy (MMPSI)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03024827
org study id: CARE-E-01
nct id: NCT03024827
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Heart Rate
time frame: Up to 6 months
measure: Blood Pressure
time frame: Up to 6 months
measure: Weight
time frame: Up to 6 months
measure: Complete Blood Count (CBC) and Differential
time frame: Up to 6 months
measure: Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)
time frame: Up to 6 months
measure: Blood Urea Nitrogen (mmol/L)
time frame: Up to 6 months
measure: Creatinine (umol/L)
time frame: Up to 6 months
measure: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)
time frame: Up to 6 months
measure: Total and Direct Bilirubin (umol/L)
time frame: Up to 6 months
measure: Albumin (g/L)
time frame: Up to 6 months
measure: Total Cholesterol and Triglyceride (mmol/L)
time frame: Up to 6 months
measure: Clobazam and Norclobazam Levels (umol/L)
time frame: Up to 6 months
description: For participants taking clobazam who become excessively sedated
measure: Clonazepam Level (umol/L)
time frame: Up to 6 months
description: For participants taking clonazepam who become excessively sedated
measure: Urine Ketones
time frame: Up to 6 months
description: For participants on the ketogenic diet
measure: Trough Level of Concomitant Anti-Convulsants
time frame: Up to 7 months
description: Measure interactions with any anti-convulsants participants may be already on
measure: Adverse Events
time frame: Through study completion, up to 7 months
description: Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea
measure: 2-hour Electroencephalogram (EEG) Recording
time frame: Up to 6 months
measure: Seizure Frequency Log Book
time frame: Through study completion, up to 7 months
measure: Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)
time frame: Through study completion, up to 7 months
measure: Cannabidiol (CBD) (ng/mL)
time frame: Up to 7 months
description: Levels in blood
measure: Tetrahydrocannabinol (Δ9-THC) (ng/mL)
time frame: Up to 7 months
description: Levels in blood
measure: 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)
time frame: Up to 7 months
description: Levels in blood
arm group label: Medical Cannabis Oil
arm group type: Experimental
description: CanniMed® 1:20
intervention type: Drug
intervention name: CanniMed® 1:20
description: A cannabidiol (CBD): tetrahydrocannabinol (Δ9 THC) 20:1 ratio product will be provided as an oil-based suspension.
arm group label: Medical Cannabis Oil
other name: Medical Cannabis Oil
criteria: 
gender: All
minimum age: 1 Year
maximum age: 10 Years
healthy volunteers: No
last name: Richard Huntsman, MD
role: Principal Investigator
affiliation: Dalhousie University
last name: Richard Tang-Wai, MD
role: Principal Investigator
affiliation: Loma Linda University
last name: Jane Alcorn, PhD
role: Principal Investigator
affiliation: University of Saskatchewan
facility: 
facility: 
facility: 
facility: 
country: Canada
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
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.
PMID: 29981580
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.
PMID: 31333569
responsible party type: Principal Investigator
investigator affiliation: University of Saskatchewan
investigator full name: Richard Huntsman
investigator title: MD
mesh term: Brain Diseases
mesh term: Epilepsy
sharing ipd: No