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The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children With Severe Epilepsy (CBD1)

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ClinicalTrials.gov Identifier: NCT02815540
Recruitment Status : Terminated (Investigator on medical leave, and difficult recruitment)
First Posted : June 28, 2016
Last Update Posted : March 4, 2019
Sponsor:
Information provided by (Responsible Party):
Gillette Children's Specialty Healthcare

Tracking Information
First Submitted Date  ICMJE June 20, 2016
First Posted Date  ICMJE June 28, 2016
Last Update Posted Date March 4, 2019
Actual Study Start Date  ICMJE February 16, 2017
Actual Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
Holter SDNN parameter change [ Time Frame: Baseline to 4 to 8 week follow up visit ]
Change from baseline Holter SDNN parameter to follow up visit Holter SDNN parameter.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
  • ECG parameters [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    Compare baseline ECG QT interval and corrected QT interval using the Bazzett formula to follow up visit ECG QT and QTc parameters
  • Holter heart rate parameters [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    Compare baseline Holter heart rate variability and time domain parameters ( RR interval, SDNN, and SDNN-i) and frequency domain parameters (VLF, HF, and LF amplitude) with follow up visit Holter heart rate parameters.
Change History Complete list of historical versions of study NCT02815540 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • Seizure frequency [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    Change from baseline seizure frequency to follow up visit seizure frequency.
  • Dysautonomia signs and symptoms [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    signs and symptoms assessed by questionnaire developed for this study that documents observable signs and symptoms of dysautonomia
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
  • Seizure frequency [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    Compare seizure frequency in those who began the study prior to taking cannabadiol with those already taking cannabadiol at baseline.
  • Dysautonomia signs and symptoms [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    Compare the frequency per day/week of signs and symptoms of dysautonomia as documented on screening questionnaire when subjects are taking cannabadiol to when subjects were not taking cannabadiol.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children With Severe Epilepsy
Official Title  ICMJE The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children
Brief Summary The investigators propose to study the effects of cannabidiol (CBD) on cardiac electrical function and the autonomic nervous system in children with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), when the CBD is administered as an artisanal oil obtained through state dispensaries or other sources. The intent is to begin to assess potential risks and benefits of this therapy in a vulnerable patient population by characterizing the effects of CBD on EKG findings, heart rate variability and the occurrence of seizures.
Detailed Description

Specific Aims/Study Objectives

This is a pilot study to explore the effects of cannabidiol (CBD) on autonomic cardiac function in children with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) when the CBD is administered as an artisanal oil. This will be achieved by addressing the following specific aims.

Aim #1: To determine the effects of CBD on cardiac function in 30 children with DS and LGS. This is the primary aim of the study: The effects of CBD on the cardiac function of 30 children with DS or LGS will be assessed using a 15-lead electrocardiogram (EKG) and a 24-hour Holter monitor. Investigators hypothesize that there will be no alterations in ventricular repolarization and heart rate variability on the EKG and Holter monitoring, respectively, after taking CBD for 4-8 weeks, compared to when participants were not taking CBD.

Note: The following aims are secondary to the primary outcome and goal of assessing the effects of CBD on cardiac function.

Aim #2: To assess signs and symptoms of dysautonomia in the presence and absence of CBD. Signs and symptoms of dysautonomia include parental perception of body temperature, skin color in hands and feet, sweating, pupil size, flushing, feeding issues, heart rate, strong emotions, constipation, urination or bowel movement issues, and irritability. These signs and symptoms will be collected using a previously-established dysautonomia survey. Investigators hypothesize there will be no change in qualitative assessments of signs and symptoms of dysautonomia after taking CBD for 4-8 weeks, compared to when participants were not taking CBD.

Aim #3: To determine the effects of CBD on the occurrence of seizures. The number of seizures in children who obtain CBD will be assessed using a 7-day seizure diary (Seizure tracker). Caregivers will record the number of seizures for a 7-day period prior to CBD administration, and repeat the seizure tracking after having received CBD for 4-8 weeks. Change in seizure numbers will be compared pre- and post-CBD administration. Investigators hypothesize that study participants will have lower seizure counts after being on CBD compared to when weren't taking CBD.

Study Design and Methodology

Study Design: Thirty patients with DS or LGS who are going to register to take medical cannabis (cannabidiol, or CBD) in the state of Minnesota will be offered the opportunity to participate in this study. If consent is obtained, the patient or guardian will be asked to complete a questionnaire developed for this study that documents observable signs and symptoms of dysautonomia, and to complete a seizure diary for 7 days prior to initially receiving the CBD. Each participant will also have a 15-lead electrocardiogram (EKG) and wear a 24-hour Holter monitor, both non-invasive measures of cardiac function, prior to being administered the CBD. The EKG and 24-hour Holter monitor will be interpreted by a cardiac electrophysiologist and will be reviewed for heart rate variability parameters. The dysautonomia questionnaire, seizure diary and cardiac measurements will be repeated 4-8 weeks after the subject has been on a stable regimen of CBD. This time-frame is based on availability of subjects schedules and clinic visits, and it is also greater than 5 half-lives previously reported for CBD (apparent half-life, 21 hours, (15)). Steady-state levels are achieved after 5 half-lives of drug dosing, thus we expect to be at steady-state concentrations.

Subjects who are already on a stable regimen of CBD, yet plan to stop taking CBD at some point for some reason, are also eligible to participate. The parent or guardian will complete the dysautonomia questionnaire and seizure diary (and research staff will be available to help with questions), and the patient will have the 15-lead EKG and 24-hour Holter monitor while still on the CBD. The subjects will then come back 4-8 weeks after their last dose of CBD to have these assessments repeated while off of the CBD. This time frame is based on availability of subjects schedules and clinic visits as well as being substantially greater than 5 half-lives of CBD, the standard wash-out period for pharmacological studies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Lennox-Gastaut Syndrome
  • Dravet Syndrome
Intervention  ICMJE
  • Procedure: 12-Lead ECG
    Subjects will be monitored while on cannabidiol with a 12-Lead ECG and/or Holter monitoring
    Other Name: Holter Monitor
  • Drug: Cannabidiol
    Subjects who are planning to take state dispensed medical cannabidiol, or are already taking state dispensed medical cannabidiol.
Study Arms  ICMJE Observational
This study looks at participants already receiving CBD from the state of MN. We are not providing the CBD. We are looking at heart function with ECGs and Holter monitoring before and after CBD is taken by the participant. We are also looking at dysautonomia signs and symptoms and seizure frequency before and after CBD is taken by the participant.
Interventions:
  • Procedure: 12-Lead ECG
  • Drug: Cannabidiol
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 Terminated
Actual Enrollment  ICMJE
 (submitted: February 28, 2019)
2
Original Estimated Enrollment  ICMJE
 (submitted: June 23, 2016)
25
Actual Study Completion Date  ICMJE December 1, 2018
Actual Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosed with Dravet syndrome or Lennox-Gastaut syndrome
  • Patients who are planning to obtain medical cannabidiol
  • Patients who are already taking medical cannabidiol and are planning to stop taking it

Exclusion Criteria:

  • Patients without a diagnosis of Dravet syndrome or Lennox-Gastaut syndrome
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 30 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 NCT02815540
Other Study ID Numbers  ICMJE CBD-001
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 Gillette Children's Specialty Healthcare
Study Sponsor  ICMJE Gillette Children's Specialty Healthcare
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Gillette Children's Specialty Healthcare
Verification Date February 2019

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