Effect of cannabidiol on sleep in developmental and epileptic encephalopathies

A total of 26 patients will be recruited from The Alfred and The Austin hospitals who are newly prescribed with EPIDYOLEX by their neurologist as part of their clinical care, but have not yet commenced. Participants will subsequently undergo two hospital admissions consisting of 24-hour EEG and polysomnography assessments at baseline, and the end of the study (16-weeks following drug initiation), respectively; actigraphy will be measured throughout the study period. Patients will be monitored with actigraphy (GENEActiv accelerometer wristwatch, ActivInsights, Kimbolton, United Kingdom) during the screening phase of 4-weeks, and if patients meet full eligibility criteria, actigraphy measurements will continue until the end of the study (week 16). Patients will be provided actigraph watches for the trial duration. Patients will be admitted to the hospital to undergo baseline concurrent 24-hour video-EEG and overnight polysomnography. Patients will be be required to be in hospital for approximately 26 hours (including the time taken for hospital admission and the set-up time). Data will be collected regarding demographics and anthropomorphic measurements (height, weight, body-mass index, and neck circumference). A minimum of 21-EEG scalp electrodes will be applied in accordance with the 10-20 International System of Electrode Placement. For the polysomnography, the following additional measurements will be added: Lead II of a standard 12 lead ECG will be used for cardiac monitoring, respiratory inductance plethysmography thoracic and abdominal bands, pulse oximetry to assess peripheral capillary oxygen saturation levels, nasal pressure, electrooculography, electromyography electrodes to the mentalis and sub-mentalis, and dual electromyography electrodes to each anterior tibialis will be added. All measurements will be recorded using Compumedics ProFusion 5 (Compumedics Limited, Abbotsford, Victoria, Australia). A qualified sleep scientist will perform the polysomnography set-up and overnight monitoring. EEG recordings will be set-up and reviewed by an accredited neurophysiology scientist, and then reported by a board-certified epileptologist. All epileptiform discharges and seizures will be annotated. Sleep staging and respiratory will be done in accordance with the latest American Academy of Sleep Medicine (AASM) guidelines. Sleep studies will be set-up, and then staged and scored by an accredited sleep scientist, and then reported by a board-certified sleep/respiratory physician. Apneas will be scored when there is a =90% reduction in airflow amplitude for =10 seconds. Hypopneas will be scored where there is a =30% reduction in airflow amplitude for =10 seconds, accompanied by either an arousal or desaturation of =3%. We will define sleep-disordered breathing as an apnea-hypopnea index (AHI) of 5 or greater, and moderate-to-severe sleep-disordered breathing as an AHI 15 or greater, and a severe sleep-disordered breathing as an AHI of 30 or greater. A diagnosis of central sleep apnea will be made if the central sleep index was 5 or greater and >50% of respiratory events were central. Sleep efficacy will be calculated as a percentage of the total sleep duration divided by the total sleep period. Patients will commence EPIDYOLEX as clinically indicated by their treating neurologist, following the baseline polysomnography. Patients will be titrated as clinically indicated at the treating clinician’s discretion to patient tolerability, in keeping with current clinical practice. Repeat 24-hour video-EEG and polysomnography will be performed at week 16. The methodology is as described for the baseline investigations, and the same reporting criteria will be applied.