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Trial registered on ANZCTR


Registration number
ACTRN12619000714189
Ethics application status
Approved
Date submitted
30/04/2019
Date registered
13/05/2019
Date last updated
20/09/2019
Date data sharing statement initially provided
13/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A single-dose, double-blind, placebo-controlled, randomised, crossover study of an oral cannabis-based medicine (ETC120) on sleep, cognition, and next-day function in adults with chronic insomnia disorder
Scientific title
A single-dose, double-blind, placebo-controlled, randomised, crossover study of an oral cannabis-based medicine (ETC120) on sleep quality and quantity in adults with chronic insomnia disorder
Secondary ID [1] 297881 0
Nil known
Universal Trial Number (UTN)
U1111-1231-0849
Trial acronym
CANSLEEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Insomnia 312254 0
Condition category
Condition code
Neurological 310802 310802 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This randomised, double-blind, placebo-controlled, crossover pilot study will assess the effects of a single dose of an oral cannabinoid medicine on sleep and next-day function relative to placebo in patients with chronic insomnia disorder.

The investigational product is an oral solution containing cannabinoids in medium-chain triglycerides (MCT) oil ('ETC120'). Participants will receive all of the interventions (a single fixed dose of ETC120 or matched placebo - both 2mL) in a randomised and counterbalanced order across two overnight sleep studies at the Woolcock Institute of Medical Research. The study investigator will instruct and directly observe the participant self-administer the dose of the oral solution via a plastic syringe, pre-filled by the study medical doctor same day.

Each overnight sleep study will be scheduled at least one-week apart to avoid any carryover effects (washout period).
Intervention code [1] 314112 0
Treatment: Drugs
Comparator / control treatment
Placebo contains the same excipient (MCT oil) as the investigational product but does not contain cannabinoids.
Control group
Placebo

Outcomes
Primary outcome [1] 319647 0
Change in total sleep time (TST) measured in minutes from in-laboratory overnight PSG
Timepoint [1] 319647 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Primary outcome [2] 319648 0
Change in wake after sleep onset (WASO) measured in minutes from in-laboratory overnight PSG
Timepoint [2] 319648 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [1] 369012 0
Average number and duration of sleep and wake bouts from in-laboratory overnight PSG.

This is a composite secondary outcome.
Timepoint [1] 369012 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [2] 369362 0
Global EEG power during NREM and REM sleep (256-channel high-density EEG during overnight PSG)

This is a composite secondary outcome.
Timepoint [2] 369362 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [3] 369363 0
Regional EEG power during NREM and REM sleep (256-channel high-density EEG during overnight PSG)

This is a composite secondary outcome.
Timepoint [3] 369363 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [4] 369364 0
Sleep spindle and slow oscillation events in NREM sleep from in-laboratory overnight PSG.

This is a composite secondary outcome.
Timepoint [4] 369364 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [5] 369365 0
Sleep micro- and macroarchitecture metrics (NREM sleep, slow wave sleep, REM sleep, arousal index, and stage shifts) from standard overnight PSG.

This is a composite secondary outcome.
Timepoint [5] 369365 0
Assessed continuously during both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [6] 369367 0
Subjective ratings of changes in sleep-wake behaviour on the Leeds Sleep Evaluation Questionnaire (LSEQ)
Timepoint [6] 369367 0
Assessed within 1 hour after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [7] 369420 0
Subjective ratings of tiredness on the Daytime Insomnia Symptom Response Scale (DISRS)
Timepoint [7] 369420 0
Assessed within 1 hour after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [8] 369421 0
Resting wake EEG power before and after sleep using high-density EEG recordings during the Karolinska Drowsiness Test (KDT) in conjunction with the Karolinska Sleepiness Scale (KSS).

This is a composite secondary outcome.
Timepoint [8] 369421 0
Assessed 30 minutes prior to sleep and 30 minutes after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [9] 369423 0
Mean latency to sleep on the Maintenance of Wakefulness Test (MWT)
Timepoint [9] 369423 0
Assessed at 10am, 12pm, 2pm, and 4pm after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [10] 369424 0
Declarative memory performance on the Word Pairs Task (WPT)
Timepoint [10] 369424 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [11] 369425 0
Procedural memory performance on the Finger Tapping Task (FTT)
Timepoint [11] 369425 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [12] 369742 0
Driving performance (measured by Oktal SCANeR Studio driving simulation software)

This is comprised of the following outcome measures:
Standard deviation of lateral position (SDLP) (measure of lane weaving)
Mean speed and standard deviation of speed
Number of lane crossings

This is a composite secondary outcome.
Timepoint [12] 369742 0
Assessed within 1 hour after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [13] 369743 0
Next-day cognitive function assessed via computerised tasks - The Stroop Task (measure of executive function)
Timepoint [13] 369743 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [14] 370311 0
Next-day cognitive function assessed via computerised tasks - Psychomotor Vigilance Task (measure of sustained attention)
Timepoint [14] 370311 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [15] 370312 0
Next-day cognitive function assessed via computerised tasks - 1- and 2-N-back Test (measure of working memory)
Timepoint [15] 370312 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [16] 370313 0
Next-day cognitive function assessed via computerised tasks - Digit Symbol Substitution Task (measure of speed of information processing)
Timepoint [16] 370313 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [17] 370314 0
Next-day cognitive function assessed via computerised tasks - Divided Attention Task (measure of working memory and attention)
Timepoint [17] 370314 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [18] 370315 0
Next-day cognitive function assessed via computerised tasks - Paced Auditory Serial Addition Task (measure of information processing and attention)
Timepoint [18] 370315 0
Assessed within 2 hours after waking at both overnight sleep studies (comparison between ETC120 versus placebo)
Secondary outcome [19] 370316 0
Plasma cannabinoid concentrations, including includes measures of THC, THC-COOH, 11-OH-THC, CBD, and endocannabinoids including 2-AG and anandamide.

This is a composite secondary outcome.
Timepoint [19] 370316 0
Blood collected within 1 hour of waking at both overnight sleep studies (comparison between ETC120 versus placebo)

Eligibility
Key inclusion criteria
1. Males and females aged 35 – 60 years old,
2. Chronic insomnia disorder diagnosed by a sleep physician or psychologist,
3. Insomnia Severity Index (ISI) score greater than or equal to 15,
4. Insomnia symptoms for more than 3 times per week and present for longer than 3 months,
5. Proficiency in English, and capable and willing to provide informed consent to the study procedures.
Minimum age
35 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Medical condition or medication that is the cause of the insomnia;
2. Known hypersensitivity to cannabinoids;
3. No reported use of cannabis within the past 3 months (or at the medical officer’s discretion) and confirmed by at least one negative urine drug screen (UDS);
4. Past or present history of cannabis dependence (ICD-10 criteria or at the medical officer’s discretion);
5. Sleep apnea (defined as Apnea Hypopnea Index [AHI] >15 and Oxygen Desaturation Index [ODI]>10) or sleep-related movement disorder based on in-laboratory polysomnography;
6. Delayed sleep phase syndrome (determined on clinical interview, actigraphy and sleep diary at screening);
7. Any medical condition related to an abnormal EEG (i.e. epilepsy, brain injury);
8. Shift-work, transmeridian travel (2 time zones) over the last one month;
9. History of major psychiatric disorder in the past 12 months except clinically-managed mild depression;
10. History of suicide attempt or current suicide ideation (score greater than 0 on Q9 to PHQ-9 at screening);
11. Current evidence of clinically significant disease [including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation], or malignancy or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments;
12. Clinically relevant cardiovascular abnormalities as determined by 12-lead electrocardiogram (ECG) at screening;
13. Pregnancy or lactation - males and females shall be advised to use reliable contraception for the duration of drug therapy and a urine pregnancy test will be performed for female participants where necessary;
14. Use of any CNS-active drugs (including antidepressants, opioids, benzodiazepines) for the past 3 months or at the medical officer’s discretion;
15. Use of medications that may have a clinically significant impact upon the metabolism and excretion of cannabinoids at the medical officer’s discretion (e.g. CYP450 enzyme inducers/inhibitors);
16. History of drug or alcohol dependency or abuse within approximately the past 2 years;
17. Urinary drug test positive for drugs (cannabis, amphetamines, and cocaine) at screening visit;
18. Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or if participant is unable to abstain from caffeine use 24 hours prior to and during each overnight sleep study;
19. Inability to refrain from alcohol consumption 24 hours prior to and during each overnight sleep study;
20. Individuals who regularly smoke or at the medical officer’s discretion;
21. Medical conditions that result in frequent need to get out of bed (e.g. nocturia);
22. Used any modality of treatment for insomnia, including CBT within 3 months before screening or at the medical doctor's discretion;
23. Unable to undergo MRI brain imaging due to implanted device (e.g. defibrillator, pacemaker) as identified via MRI screening questionnaire;
24. Required to complete mandatory drug testing (e.g. workplace testing, court order).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After obtaining informed consent, participants will be randomly allocated to order of treatment. Method of allocation concealment will involve numbered containers and central randomisation by computer. Allocation concealment will only be known by the drug distributer and an independent study investigator, neither of whom have direct contact with the participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by computer software (i.e. computerised sequence generation), and by the order of participant enrolment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13547 0
Woolcock Institute of Medical Research - Glebe
Recruitment postcode(s) [1] 26170 0
2037 - Glebe

Funding & Sponsors
Funding source category [1] 302406 0
University
Name [1] 302406 0
The Lambert Initiative for Cannabinoid Therapeutics, University of Sydney
Address [1] 302406 0
Level 6, Building M02F, Brain and Mind Centre, 94 Mallett Street Camperdown NSW 2050
Country [1] 302406 0
Australia
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
431 Glebe point Road, 2037, NSW, Glebe
Country
Australia
Secondary sponsor category [1] 302398 0
None
Name [1] 302398 0
Address [1] 302398 0
Country [1] 302398 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303075 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 303075 0
129 Glen Osmond Road Eastwood, Adelaide, South Australia 5063
Ethics committee country [1] 303075 0
Australia
Date submitted for ethics approval [1] 303075 0
Approval date [1] 303075 0
29/03/2019
Ethics approval number [1] 303075 0
2018-04-284

Summary
Brief summary
Anecdotally, cannabis is frequently reported by consumers to promote sleep. Indeed, a recent Australian survey found that sleep disorders were the fourth most indicated reason for using cannabis for medicinal reasons in a community sample of 1,700 users (Lintzeris et al., 2018). While improved sleep is one of the positive effects that cannabis users typically report, there is limited well-designed research using objective measures assessing the effects of cannabis on sleep quality and quantity. Moreover, no study to-date has examined the effects of cannabinoid medicine in people with chronic insomnia disorder.

To address this gap, we will investigate the acute effects of a cannabinoid medicine (ETC120) on sleep and next-day function compared to placebo in patients with chronic insomnia disorder. This study will utilise novel high-density 256-channel EEG coupled with structural MRI to examine and localise differences in sleep depth and brain activation during both sleep and wakefulness following a single dose of ETC120 and placebo during an overnight sleep study. Daytime function including cognition, alertness and driving performance will also be assessed.

As this is a pilot study, we aim to recruit 20 patients aged 35-60 years inclusive with a diagnosis of chronic insomnia disorder. Participants will be comprehensively screened for eligibility across 1-2 visits at the Woolcock Institute of Medical Research, Sydney. All participants will receive all of the interventions in a randomised and counterbalanced order during two overnight sleep studies at the sleep laboratory at the Woolcock Institute of Medical Research. Each overnight sleep study will take approximately 24 hours to complete and will be scheduled at least one-week apart to avoid any carryover effects.

This aim of this study is to provide high-quality pilot data using novel multimodal neuroimaging technologies to comprehensively examine the acute effects of a cannabinoid medicine on sleep in patients with chronic insomnia disorder.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92378 0
Prof Ronald Grunstein
Address 92378 0
Woolcock Institute of Medical Research, 431 Glebe point Road, 2037, NSW, Glebe
Country 92378 0
Australia
Phone 92378 0
+61 2 9114 0438
Fax 92378 0
Email 92378 0
ron.grunstein@sydney.edu.au
Contact person for public queries
Name 92379 0
Miss Anastasia Suraev
Address 92379 0
Woolcock Institute of Medical Research, 431 Glebe point Road, 2037, NSW, Glebe
Country 92379 0
Australia
Phone 92379 0
+61 2 9114 0452
Fax 92379 0
Email 92379 0
anastasia.suraev@sydney.edu.au
Contact person for scientific queries
Name 92380 0
Dr Camilla Hoyos
Address 92380 0
Woolcock Institute of Medical Research, 431 Glebe point Road, 2037, NSW, Glebe
Country 92380 0
Australia
Phone 92380 0
+61 2 9114 0409
Fax 92380 0
Email 92380 0
camilla.hoyos@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results