The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study

Darren Reithmeier, Richard Tang-Wai, Blair Seifert, Andrew W Lyon, Jane Alcorn, Bryan Acton, Scott Corley, Erin Prosser-Loose, Darrell D Mousseau, Hyun J Lim, Jose Tellez-Zenteno, Linda Huh, Edward Leung, Lionel Carmant, Richard J Huntsman, Darren Reithmeier, Richard Tang-Wai, Blair Seifert, Andrew W Lyon, Jane Alcorn, Bryan Acton, Scott Corley, Erin Prosser-Loose, Darrell D Mousseau, Hyun J Lim, Jose Tellez-Zenteno, Linda Huh, Edward Leung, Lionel Carmant, Richard J Huntsman

Abstract

Background: Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life.

Methods: Twenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10 years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects.

Discussion: This paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids.

Trial registration: https://ichgcp.net/clinical-trials-registry/NCT03024827" title="See in ClinicalTrials.gov">NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: https://ichgcp.net/clinical-trials-registry/NCT03024827.

Keywords: Cannabidiol; Cannabis; CanniMed®; Pediatric epilepsy.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval was obtained from the University of Saskatchewan Ethics Review Board for Biomedical Research in Human Subjects and operational approval to conduct this study was obtained from the Saskatchewan Health Authority. Similar Biomedical Ethics approvals have been obtained from the participating sites (University of British Columbia, Universite de Montreal, University of Manitoba). Approval from Health Canada was obtained for use of the study product and to conduct this study.

Prior to enrollment informed consent will be obtained from the participant’s parents or legal guardians. Participants who were felt to be capable of providing assent were asked to provide their written and verbal assent to participate in the study.

Consent for publication

Not applicable.

Competing interests

All authors declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
A flow chart of participant enrollment, treatment with CBD-Enriched Cannabis herbal extract, monitoring and weaning

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