University of Alabama at Birmingham (UAB) Pediatric CBD Program
Condition: Epilepsy; Seizures
MeSH terms: Seizures
Intervention: Epidiolex
Intervention description: Epidiolex oral solution (100 mg/mL CBD concentration) with inactive ingredients including anhydrous ethanol, sesame seed oil, strawberry flavor, and sucralose).
Intervention MeSH terms: Cannabidiol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 89.0
Sex: All
Minimum age: 1 Year
Maximum age: 19 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety and tolerability of Epidiolex at various
      doses between 5 mg/kg/day and 50 mg/kg/day as an additional (add-on) drug for treating
      debilitating, drug-resistant epilepsy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients between 1 years (12 months)-18 years with drug resistant epilepsy confirmed
             by video EEG recording report, and

          -  Patient should have history of a trial of at least four anti-epileptic drugs (AEDs),
             including one trial of a combination of two concomitant drugs without successful
             seizure control. Vagal nerve stimulation (VNS), Responsive Neurostimulation (RNS) deep
             brain stimulation, or the ketogenic diet can be considered equivalent to a drug trial.
             Patient suffering from an epileptic syndrome that is known to be refractory to
             treatment, such as Dravet or Lennox-Gastaut Syndrome, may be included after a trial of
             only two drugs, and

          -  Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4 weeks
             prior to submitting records for review by the CBD Treatment Approval Committee.

          -  VNS or RNS must be on stable settings for a minimum of 3 months.

          -  If on ketogenic diet, must be on stable ration for a minimum of 3 months.

          -  Review of the following patient medical information:

               -  Most recent Brain MRI report,

               -  Most recent ECG report,

               -  Video/EEG monitoring report confirming the diagnosis of epilepsy,

               -  Evidence that the patient has failed 4 AEDs as indicated above,

               -  Patient must have at least 4 clinically countable seizures per month,

               -  Seizure history to include a documented history of generalized (drop, atonic,
                  tonic clonic, and/or myoclonic) seizures, focal seizures without loss of
                  consciousness with a motor component, focal seizures with loss of consciousness,
                  or focal seizures with secondary generalization, complex partial seizures with a
                  motor or tonic component, and I or altered awareness seizures,

               -  Results of routine testing including blood work (Complete Blood Count (CBC),
                  Comprehensive Metabolic Panel (CMP), Liver Function Tests (LFTs), renal panel,
                  Urinary Analysis (UA), and levels of all AEDs) and digital copy of a routine EEG
                  along with the formal written report performed within 3 months prior to
                  submitting records for CBD Treatment Approval review. If applicable, results of
                  any metabolic or genetic testing performed should be included in submitted
                  records for review. If any AED dose was adjusted in the preceding 3 months, level
                  on the new dose will need to be provided.

               -  If applicable, documentation (including date of surgery) of prior VNS, RNS,
                  Corpus Callosotomy, or other epilepsy surgery the patient has received.

          -  Acceptable method of contraception (or abstinence) for women of childbearing potential
             and for male patients with partners of childbearing potential, and female patients
             must have a negative urine pregnancy test on the day of initiating CBD.

          -  For patients who agree to participate in the optional neuroimaging sub-study, an MRI
             screen will be obtained to show that the patient does not have contraindication to
             receiving MRI/functional MRI (fMRI) at 3 Tesla (e.g., metallic artifact).

          -  Patients are able to supply investigator with seizure calendars for the past 3 months
             prior to submitting records for CBD Treatment Approval Committee review. The patient
             will need to provide an updated calendar at the time of enrollment.

          -  Approval for inclusion by the CBD Treatment Approval Committee.

          -  Current State of Alabama Resident

          -  Acceptable documentation of Alabama residency includes the following:

               -  a state issued identification (ID), such as a driver's license, from patient or
                  patient's parent/ legally authorized representative (LAR).

               -  documents showing the patient or patient's parent/LAR rents/owns property in the
                  state,

               -  state voter registration from patient or patient's parent/LAR, or

               -  a recent state tax return from patient or patient's parent/LAR.

        Exclusion Criteria:

          -  Active Psychogenic non-epileptic seizures (PNES); Patients with more than 1 year
             freedom from PNES will not be excluded,

          -  Patients who are pregnant, breastfeeding, or not using acceptable methods of
             contraception during the course of the study and for three months thereafter,

          -  Male patient's partner is of child bearing potential; unless willing to ensure that
             they (male patients) or their partner(s) are using acceptable methods of contraception
             during the course of the study and for three months thereafter

          -  History of substance abuse/addiction,

          -  Use of medical marijuana or CBD based product in the past 30 days,

          -  Initiation of felbamate within last 12 months,

          -  Allergy to CBD or any marijuana-type products,

          -  Alanine Aminotransferase (ALT) >5 x Upper Limit of Normal (ULN) or Aspartate
             Aminotransferase (AST) >5 x ULN, as seen in participant's laboratory results submitted
             to the CBD Treatment Approval Committee for review.

          -  Hemoglobin <10 or Hematocrit <30 or White Blood Cell (WBC) < 2000, as seen in
             participant's laboratory results submitted to the CBD Treatment Approval Committee for
             review.

          -  In Investigator's judgement, active medical condition/treatment that impacts study
             activities.

          -  Unable to provide consent (and no LAR),

          -  Unable/Failure to comply with study visits/requirements and/or instructions.

          -  Confirmed diagnosis for Dravet Syndrome or Lennox-Gastaut Syndrome that qualifies the
             patient for a Greenwich (GW) Dravet Syndrome or Lennox-Gastaut Syndrome randomized
             controlled clinical trial for which the patient is eligible pursuant to the GW
             clinical trial enrollment criteria unless

               -  (a) there is no study that is either actively open for enrollment of patients at
                  The University of Alabama at Birmingham (UAB) or that is expected to actively
                  begin enrolling patients at UAB within two (2) months of the date on which the
                  patient is screened for the UAB Pediatric CBD Program or UAB Adult CBD Program.
                  Primary residence in a State different than Alabama.

          -  Subjects with contraindications to MRI/fMRI at 3 Tesla (e.g., metallic artifact) will
             not be offered participation in the optional sub-study.