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University of Alabama at Birmingham (UAB) Pediatric CBD Program

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02695537
Recruitment Status : Completed
First Posted : March 1, 2016
Results First Posted : April 10, 2020
Last Update Posted : April 10, 2020
Sponsor:
Information provided by (Responsible Party):
Martina Bebin, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE February 24, 2016
First Posted Date  ICMJE March 1, 2016
Results First Submitted Date  ICMJE February 27, 2020
Results First Posted Date  ICMJE April 10, 2020
Last Update Posted Date April 10, 2020
Actual Study Start Date  ICMJE April 2015
Actual Primary Completion Date February 27, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2020)
  • Number of Participants With Severe Adverse Events (Increase in Seizure Frequency by More Than 100% Leading to Emergency Room Visit or Hospitalization). [ Time Frame: For 1 Year following Enrollment ]
    Severe adverse events (SAEs) were defined as increase in seizure frequency by more than 100% leading to emergency room visit or hospitalization. During study clinic and phone visits, adverse and severe adverse event monitoring and reporting were assessed among all participants. Data was recorded and stored in the UAB RedCap System.
  • Number of Participants With Change in Resting Blood Pressure or Heart Rate by 25% if Considered Significant by Managing Neurologist. [ Time Frame: For 1 Year following Enrollment ]
    During study clinic visits, participant vital signs, including blood pressure and heart rate, were collected. Data was recorded and stored in the UAB RedCap System. Clinically significant was determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above were considered clinically significant. Adverse events grade 4 or above were considered severe adverse events.
  • Number of Participants With Change in Laboratory Tests Considered by Managing Neurologists as Clinically Significant. [ Time Frame: For 1 Year following Enrollment ]
    During study clinic visits, participants received laboratory testing to assess for side effects and toxicity. Data was recorded and stored in the UAB RedCap System. Laboratory testing included Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP; included Liver Function Tests (LFTs) mainly looking at alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), Urine Analysis (UA), and Antiepileptic Drug (AED) levels. Clinically significant was determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above were considered clinically significant. Adverse events grade 4 or above were considered severe adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: February 29, 2016)
  • Evaluate severe adverse events (increase in seizure frequency by more than 25% or any hospitalization related to increase in seizure frequency) [ Time Frame: 1 year ]
  • Evaluate change in resting blood pressure or heart rate by 25% [ Time Frame: 1 year ]
  • Evaluate any change in, CBC, CMP, Liver function tests (LFTSs ), Urinary Analysis or Antiepileptic drug (AED) levels considered by managing neurologists as clinically significant. [ Time Frame: 1 year ]
    Clinically significant will be determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above will be considered clinically significant. Adverse Events graded 4 or above will be considered severe adverse events (SAE)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2020)
  • Change in Seizure Frequency as Measured in Total Number of Seizures Per Month. [ Time Frame: For 1 Year following Enrollment ]
    Participants were given seizure diary logs and dairy data collection was done at study clinic visits. Data was recorded and stored in the UAB RedCap System. The analysis plan was to assess the pattern of change in seizure frequency over time, relative to baseline, following CBD exposure. Since the baseline measure was reported at the time of screening, there was some tendency to overestimate the frequency of seizures in the historically reported interval. This was examined by comparing the initial study visits improvement versus the pattern of control over time, and was assessed using graphic techniques and summary statistics.
  • Change in Seizure Severity Measured by the Chalfont Seizure Severity Scale (Duncan & Sander, 1991, JNNP). [ Time Frame: For 1 Year following Enrollment ]
    Seizure severity was collected during study clinic and phone visits using the Chalfont Seizure Severity Scale (CSSS) (Duncan & Sander, 1991, JNNP) through verbal reporting. The CSSS measured components of seizures most disturbing or disruptive to the participants. The total scores for a given seizure type was its severity score. High scores indicated high severity of the seizures (no fixed maximum value), while a score of zero indicated low severity. Scores were recorded and stored in the UAB RedCap System. The analysis plan was to assess the pattern of change in seizure severity scores over time, relative to baseline, following CBD exposure. Since the baseline measure was reported at the time of screening, there was some tendency to overestimate the severity of seizures in the historically reported interval. This was examined by comparing the initial study visits improvement versus the pattern of control over time, and was assessed using graphic techniques and summary statistics.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 29, 2016)
  • Assess the frequency in decrease in seizure frequency as measured in total number of seizures per month. [ Time Frame: 30 days ]
  • Assess the frequency in decrease in seizure severity as measured by the Chalfont Seizure Severity Scale (Duncan & Sander, 1991, JNNP). [ Time Frame: 30 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE University of Alabama at Birmingham (UAB) Pediatric CBD Program
Official Title  ICMJE University of Alabama at Birmingham (UAB) Pediatric CBD Program
Brief 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.
Detailed Description

The specific goals of this phase I dose finding study, conducted in consecutively enrolled patients 1-19 years of age, are to prospectively and longitudinally assess the safety and tolerability, including cognitive effects, of Cannabidiol (CBD) at various doses between 5 mg/kg/day and 25 mg/kg/day, with additional titration in some cases up to 50 mg/kg/day. In order to participate in the study, participants will need to fulfill the inclusion and exclusion criteria.

The goal of the study is to fulfill the mandate of "Carly's Law" and to provide patients with debilitating epileptic conditions with access to CBD as an add-on treatment. Other care including routine neurological care unrelated to participation in the CBD study will need to be provided by patients' primary/current treating neurologist.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epilepsy
  • Seizures
Intervention  ICMJE Drug: Epidiolex
Epidiolex oral solution (100 mg/mL CBD concentration) with inactive ingredients including anhydrous ethanol, sesame seed oil, strawberry flavor, and sucralose).
Other Names:
  • Cannabidiol
  • CBD
Study Arms  ICMJE Experimental: Epidiolex 100 milligram/milliliter (mg/mL) oral solution

Participants will receive a CBD starting dose of 5 mg/kg/day in twice daily dosing and titrate by 5 mg/kg/2 weeks up to 25 mg/kg/day. Additional increases in dosing, by 5 mg/kg/day up to a maximum of 50 mg/kg/day, may be instituted at the discretion of the treating Principle Investigator (PI).

If a subject experiences a "clinically significant" or "dose limiting" adverse event (AE) or severe adverse event (SAE) attributable to CBD, the investigator will determine if a dose reduction or taper is necessary (decreases will occur in 5 mg/kg/2 week increments or at a rate felt appropriate by the treating PI).

Intervention: Drug: Epidiolex
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: December 18, 2019)
89
Original Estimated Enrollment  ICMJE
 (submitted: February 29, 2016)
100
Actual Study Completion Date  ICMJE February 27, 2019
Actual Primary Completion Date February 27, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02695537
Other Study ID Numbers  ICMJE IRB-140905010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Martina Bebin, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Martina Bebin, MD Neurology Chair Office - University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date March 2020

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