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

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Dravet Syndrome
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Brief Title

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

Official Title

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 Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Holter SDNN Parameter Change

Secondary Outcome

 Seizure Frequency

Condition

Lennox-Gastaut Syndrome

Intervention

12-Lead ECG

Study Arms / Comparison Groups

 Observational
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Procedure

Estimated Enrollment

2

Start Date

February 16, 2017

Completion Date

December 1, 2018

Primary Completion Date

December 1, 2018

Eligibility Criteria

        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

Gender

All

Ages

2 Years - 30 Years

Accepts Healthy Volunteers

No

Contacts

Beverly S Wical, MD, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT02815540

Organization ID

CBD-001

Responsible Party

Sponsor

Study Sponsor

Gillette Children's Specialty Healthcare

Study Sponsor

Beverly S Wical, MD, Principal Investigator, Gillette Children's Specialty Healthcare

Verification Date

December 2021