Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: 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

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.

Condition or disease Intervention/treatment Phase
Lennox-Gastaut Syndrome Dravet Syndrome Procedure: 12-Lead ECG Drug: Cannabidiol Phase 1 Phase 2

  Hide Detailed Description

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children
Actual Study Start Date : February 16, 2017
Actual Primary Completion Date : December 1, 2018
Actual Study Completion Date : December 1, 2018


Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Seizure frequency [ Time Frame: Baseline and 4 to 8 week follow up visit ]
    Change from baseline seizure frequency to follow up visit seizure frequency.

  2. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02815540


Locations
Layout table for location information
United States, Minnesota
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, United States, 55101
Sponsors and Collaborators
Gillette Children's Specialty Healthcare

Publications:
1. Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Severe myoclonic epilepsy in infancy (Dravet syndrome). In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P (eds) Epileptic syndromes in infancy, childhood and adolescence, 4th ed. John Libbey, London, 2005, pp 89 - 109.
2. http://www.ninds.nih.gov/disorders/lennoxgastautsyndrome/lennoxgastautsyndrome.htm, Retrieved 6.10.2015
7. Wical, B, Wendorf H, Leighty D, Tervo M, Tervo R. Signs of Dysautonomia in Children with Dravet Syndrome. Presented at the Annual Meeting of the American Epilepsy Society, Boston, MA, Dec 2009.
15. Ohlsson A, Lindgren JE, Andersson S, Agurell S, Gillespie H, Hollister L. (1984). Single dose kinetics of cannabidiol in man. Cannabinoids: chemical, pharmacologic, and therapeutic aspects. S. Agurell, W. L. Dewey and R. Willette. Orlando, FL, Academic Press Inc.: 219-225. doi: 10.1016/B978-0-12-044620-9.50003-8

Layout table for additonal information
Responsible Party: Gillette Children's Specialty Healthcare
ClinicalTrials.gov Identifier: NCT02815540     History of Changes
Other Study ID Numbers: CBD-001
First Posted: June 28, 2016    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Lennox Gastaut Syndrome
Epilepsies, Myoclonic
Disease
Pathologic Processes
Epileptic Syndromes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Epilepsy, Generalized
Epidiolex
Anticonvulsants