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

NCT ID: NCT02815540

Last Updated: 2022-08-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-16

Study Completion Date

2018-12-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lennox-Gastaut Syndrome Dravet Syndrome

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Heart Function and Dysautonomia

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.

Group Type OTHER

12-Lead ECG

Intervention Type PROCEDURE

Subjects will be monitored while on cannabidiol with a 12-Lead ECG and/or Holter monitoring

Cannabidiol

Intervention Type DRUG

Subjects who are planning to take state dispensed medical cannabidiol, or are already taking state dispensed medical cannabidiol.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

12-Lead ECG

Subjects will be monitored while on cannabidiol with a 12-Lead ECG and/or Holter monitoring

Intervention Type PROCEDURE

Cannabidiol

Subjects who are planning to take state dispensed medical cannabidiol, or are already taking state dispensed medical cannabidiol.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Holter Monitor

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

2 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Gillette Children's Specialty Healthcare

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Beverly S Wical, MD

Role: PRINCIPAL_INVESTIGATOR

Gillette Children's Specialty Healthcare

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND

2. http://www.ninds.nih.gov/disorders/lennoxgastautsyndrome/lennoxgastautsyndrome.htm, Retrieved 6.10.2015

Reference Type BACKGROUND

Sakauchi M, Oguni H, Kato I, Osawa M, Hirose S, Kaneko S, Takahashi Y, Takayama R, Fujiwara T. Mortality in Dravet syndrome: search for risk factors in Japanese patients. Epilepsia. 2011 Apr;52 Suppl 2:50-4. doi: 10.1111/j.1528-1167.2011.03002.x.

Reference Type BACKGROUND
PMID: 21463280 (View on PubMed)

Skluzacek JV, Watts KP, Parsy O, Wical B, Camfield P. Dravet syndrome and parent associations: the IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief. Epilepsia. 2011 Apr;52 Suppl 2:95-101. doi: 10.1111/j.1528-1167.2011.03012.x.

Reference Type BACKGROUND
PMID: 21463290 (View on PubMed)

Jehi L. Sudden death in epilepsy, surgery, and seizure outcomes: the interface between heart and brain. Cleve Clin J Med. 2010 Jul;77 Suppl 3:S51-5. doi: 10.3949/ccjm.77.s3.09.

Reference Type BACKGROUND
PMID: 20622077 (View on PubMed)

Kalume F. Sudden unexpected death in Dravet syndrome: respiratory and other physiological dysfunctions. Respir Physiol Neurobiol. 2013 Nov 1;189(2):324-8. doi: 10.1016/j.resp.2013.06.026. Epub 2013 Jul 9.

Reference Type BACKGROUND
PMID: 23850567 (View on PubMed)

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.

Reference Type BACKGROUND

Delogu AB, Spinelli A, Battaglia D, Dravet C, De Nisco A, Saracino A, Romagnoli C, Lanza GA, Crea F. Electrical and autonomic cardiac function in patients with Dravet syndrome. Epilepsia. 2011 Apr;52 Suppl 2:55-8. doi: 10.1111/j.1528-1167.2011.03003.x.

Reference Type BACKGROUND
PMID: 21463281 (View on PubMed)

Nei M, Sperling MR, Mintzer S, Ho RT. Long-term cardiac rhythm and repolarization abnormalities in refractory focal and generalized epilepsy. Epilepsia. 2012 Aug;53(8):e137-40. doi: 10.1111/j.1528-1167.2012.03561.x. Epub 2012 Jun 18.

Reference Type BACKGROUND
PMID: 22709423 (View on PubMed)

Ergul Y, Ekici B, Tatli B, Nisli K, Ozmen M. QT and P wave dispersion and heart rate variability in patients with Dravet syndrome. Acta Neurol Belg. 2013 Jun;113(2):161-6. doi: 10.1007/s13760-012-0140-z. Epub 2012 Oct 13.

Reference Type BACKGROUND
PMID: 23065439 (View on PubMed)

Granjeiro EM, Gomes FV, Guimaraes FS, Correa FM, Resstel LB. Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress. Pharmacol Biochem Behav. 2011 Oct;99(4):743-8. doi: 10.1016/j.pbb.2011.06.027. Epub 2011 Jul 12.

Reference Type BACKGROUND
PMID: 21771609 (View on PubMed)

Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schroder N, Nardi AE, Martin-Santos R, Hallak JE, Zuardi AW, Crippa JA. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011 May;36(6):1219-26. doi: 10.1038/npp.2011.6. Epub 2011 Feb 9.

Reference Type BACKGROUND
PMID: 21307846 (View on PubMed)

Martin-Santos R, Crippa JA, Batalla A, Bhattacharyya S, Atakan Z, Borgwardt S, Allen P, Seal M, Langohr K, Farre M, Zuardi AW, McGuire PK. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Des. 2012;18(32):4966-79. doi: 10.2174/138161212802884780.

Reference Type BACKGROUND
PMID: 22716148 (View on PubMed)

Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014 Mar 5;2014(3):CD009270. doi: 10.1002/14651858.CD009270.pub3.

Reference Type BACKGROUND
PMID: 24595491 (View on PubMed)

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

Reference Type BACKGROUND

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CBD-001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

CBD Cannabis Extract: Pharmacokinetic Studies
NCT04280289 COMPLETED EARLY_PHASE1
Ketogenic Diet Program for Epilepsy
NCT02497105 COMPLETED NA