Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000855628p
Ethics application status
Submitted, not yet approved
Date submitted
29/06/2023
Date registered
8/08/2023
Date last updated
8/08/2023
Date data sharing statement initially provided
8/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of cannabidiol on sleep in developmental and epileptic encephalopathies
Scientific title
An evaluation of cannabidiol on sleep and how this relates to epileptic electroencephalogram abnormalities and seizures in adults with Lennox-Gastaut Syndrome and Dravet Syndrome
Secondary ID [1] 310012 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 330518 0
Condition category
Condition code
Neurological 327370 327370 0 0
Epilepsy

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
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.
Intervention code [1] 326434 0
Diagnosis / Prognosis
Comparator / control treatment
There is no comparator or control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335236 0
Any change in sleep quality in patients with Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS) taking cannabidiol will be assessed by a change in cortical arousal index.
Timepoint [1] 335236 0
16 weeks post commencement of cannabidiol therapy.
Secondary outcome [1] 423576 0
Any change in seizure frequency in patients with LGS and DS taking cannabidiol may be determined by a change in the cortical arousal index.
Timepoint [1] 423576 0
16 weeks post commencement of cannabidiol therapy.

Eligibility
Key inclusion criteria
Participants will be eligible to be included in the study if all the following criteria apply:
• Aged 18 to 60 years;
• Diagnosis of Dravet syndrome or Lennox-Gastaut syndrome and prescribed, but have not yet commenced EPIDYOLEX as part of their routine clinical care by their neurologist;
• Stable epilepsy treatment (pharmacotherapy treatment, ketogenic diet, vagal nerve stimulation or deep brain stimulation) for at least 4 weeks prior to treatment initiation; and
• Written informed consent obtained from the participant prior to any study-related procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
• Current treatment with cannabis-based products;
• Unstable hepatic or renal disease;
• Epilepsy surgery, or vagal nerve stimulation/deep brain stimulation implantation in the past 6-months; or
• Patients treated with continuous positive airway pressure (CPAP) .

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
For primary and secondary endpoints, we will conduct a Student’s t-test or Mann-Whitney U test, where appropriate. Safety and tolerability outcomes, such as adverse events, will be descriptively summarized. All statistical tests will be performed by using Stata version 16.1 (StataCorp, TX).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/08/2023
Actual
Date of last participant enrolment
Anticipated
19/02/2024
Actual
Date of last data collection
Anticipated
19/08/2024
Actual
Sample size
Target
26
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 40658 0
3000 - Melbourne
Recruitment postcode(s) [2] 40659 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 314189 0
Commercial sector/Industry
Name [1] 314189 0
Jazz Pharmaceuticals
Country [1] 314189 0
United States of America
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road
Melbourne 3004
Victoria, Australia
Country
Australia
Secondary sponsor category [1] 316108 0
None
Name [1] 316108 0
Address [1] 316108 0
Country [1] 316108 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313315 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313315 0
55 Commercial Road
Melbourne 3004
Victoria, Australia
Ethics committee country [1] 313315 0
Australia
Date submitted for ethics approval [1] 313315 0
26/06/2023
Approval date [1] 313315 0
Ethics approval number [1] 313315 0

Summary
Brief summary
This is a multi-centre, prospective, cohort study to evaluate epileptic encephalogram abnormalities and seizures in relation to sleep measures using polysomnography in patients diagnosed with an epileptic encephalopathy (Dravet syndrome and LGS) during video-EEG monitoring admission and are undergoing treatment with cannabidiol (EPIDYOLEX) as part of their routine clinical care. A total of 26 patients will be recruited from The Alfred and The Austin hospitals who are newly prescribed with EPIDYOLEX but have not yet commenced. The study will consist of a 4-week baseline period prior to drug initiation, during which time participants will keep a seizure diary and undergo actigraphy (GENEActiv accelerometer wristwatch) measurements. 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. All medications or interventions for epilepsy will remain unchanged the 4-weeks during the screening period and throughout the study period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127710 0
Dr Shobi Sivathamboo
Address 127710 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne 3004
Victoria, Australia
Country 127710 0
Australia
Phone 127710 0
+61 3 9903 0924
Fax 127710 0
Email 127710 0
Shobi.Sivathamboo@monash.edu
Contact person for public queries
Name 127711 0
Dr Shobi Sivathamboo
Address 127711 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne 3004
Victoria, Australia
Country 127711 0
Australia
Phone 127711 0
+61 3 9903 0924
Fax 127711 0
Email 127711 0
Shobi.Sivathamboo@monash.edu
Contact person for scientific queries
Name 127712 0
Dr Shobi Sivathamboo
Address 127712 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne 3004
Victoria, Australia
Country 127712 0
Australia
Phone 127712 0
+61 3 9903 0924
Fax 127712 0
Email 127712 0
Shobi.Sivathamboo@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This data is not able to be shared beyond the authorised research team due to the agreement between parties.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.