CUPID: Cannabinol Use in Patients With Insomnia Disorder
Study Details
Study Description
Brief Summary
This study aims to investigate the acute effects of cannabinol (CBN) 30 mg and 300 mg, versus placebo, on sleep architecture and next-day functioning in adults aged 25-65 years with chronic insomnia disorder.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a randomised, double-blind, placebo-controlled, three-arm, crossover, single-centre, proof-of-concept study in twenty participants with chronic insomnia disorder (as per clinician diagnosis and Insomnia Severity Index [ISI] Score ≥15). Across three overnight treatment sessions, participants will receive single dose oral liquid 30 mg cannabinol (CBN), 300 mg CBN, and matched placebo. Participants will undergo overnight sleep assessment using in-laboratory polysomnography (PSG) to examine CBN-related changes to sleep parameters; and various objective and subjective measures of sleep and next-day neurobehavioral function. Each treatment session will be separated by the two-week washout period.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 30 mg Cannabinol (CBN) Single fixed dose administered 2 hours prior to habitual sleep onset. |
Drug: 30 mg Cannabinol (CBN)
Participants will receive a 2 mL oral dose of 'ECS 310' (1.5%), an oral formulation of CBN (15 mg/mL) suspended in medium chain triglycerides (MCT) oil.
Other Names:
|
| Experimental: 300 mg Cannabinol (CBN) Single fixed dose administered 2 hours prior to habitual sleep onset. |
Drug: 300 mg Cannabinol (CBN)
Participants will receive a 2 mL oral dose of 'ECS 310' (15%), an oral formulation of CBN (150 mg/mL) suspended in medium chain triglycerides (MCT) oil.
Other Names:
|
| Placebo Comparator: Placebo Single fixed dose administered 2 hours prior to habitual sleep onset. |
Drug: Placebo
Participants will receive a 2 mL oral dose of placebo. Placebo contains the same excipient, medium chain triglycerides (MCT) oil, as the investigational products but does not contain cannabinoids.
|
Outcome Measures
Primary Outcome Measures
- Wake After Sleep Onset (WASO) [Night 1]
WASO minutes measured using overnight in-laboratory polysomnography. WASO is calculated from the first epoch after lights out until the last epoch scored as any stage of sleep by a polysomnographic technician in accordance with AASM Sleep Scoring criteria.
Secondary Outcome Measures
- Traditional sleep staging [Night 1]
Proportion of the sleep opportunity scored as the 5 stages (wake, and N1, N2, N3, and rapid eye movement [REM] sleep) between lights out and lights on, measured using overnight in-laboratory polysomnography, scored by polysomnographic technician in accordance with AASM Sleep Scoring criteria.
- Sleep Onset Latency (SOL) [Night 1]
SOL minutes measured using in-laboratory polysomnography. SOL is calculated from time of lights out until to the first sleep epoch scored by polysomnographic technician in accordance with AASM Sleep Scoring criteria.
- Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep. [Night 1]
Spectral power of delta (1-4.5Hz), theta (4.5-8Hz), alpha (8-12Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography after artefacts are detected and removed.
Other Outcome Measures
- Sleep Spindles During Non-Rapid Eye Movement (NREM) Sleep. [Night 1]
Sleep spindle and slow oscillation events in NREM sleep from in-laboratory overnight PSG. A sleep spindle detection algorithm will be applied to EEG signals from polysomnography after artefacts are detected and removed.
- Arousal Index [Night 1]
Number of cortical arousals captured via the electroencephalogram per hour of sleep scored by the polysomnographic technician on the polysomnogram in accordance with AASM Sleep Scoring criteria.
- Absolute Electroencephalography (EEG) Power During Rapid Eye Movement (REM) Sleep. [Night 1]
Spectral power of delta (1-4.5Hz), theta (4.5-8Hz), alpha (8-12Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography after artefacts are detected and removed.
- Next day post-wake subjective sleep evaluation [Morning after drug administration]
Leeds Sleep Evaluation Questionnaire (LSEQ) score.
- Standard Deviation of Lateral Position (SDLP) During Next Day Post-Wake Driving (Safety outcome) [Morning after drug administration]
Driving performance measured using a fixed-based driving simulator (SCANeR Studio Simulation Engine, AVSimulation) equipped with standard vehicle controls and a custom-built scenario.
- Speed During Next During Next Day Post-Wake Drive (Safety outcome) [Morning after drug administration]
Driving performance measured using a fixed-based driving simulator (SCANeR Studio Simulation Engine, AVSimulation) equipped with standard vehicle controls and a custom-built scenario. Average speed and standard deviation in absolute speed compared to target speed will be analysed.
- Reaction Time During Next During Next Day Post-Wake Drive (Safety outcome) [Morning after drug administration]
Driving performance measured using a fixed-based driving simulator (SCANeR Studio Simulation Engine, AVSimulation) equipped with standard vehicle controls and a custom-built scenario. Reaction time to brake in response to secondary stimuli in milliseconds will be analysed.
- Absolute Electroencephalographic (EEG) Power during next day post-wake driving simulator task. (Safety outcome) [Morning after drug administration]
Spectral power of delta (1-4.5Hz), theta (4.5-8Hz), alpha (8-12Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography after artefacts are detected and removed.
- Subjective Mood Evaluation (Safety outcome) [Immediately after and morning after drug administration]
The Abbreviated Profile of Mood States (POMS) consists of 37 items measuring domains of 'tension', 'depressed', 'anger', 'vigour', 'fatigue' and 'concentration'. Participants respond to each item using 5-point Likert scales ranging from 0 (Not at all) to 4 (Extremely). Composite scores are calculated by summing scores and subtracting 'vigour' scores. Higher scores are indicative of better mood. Change from pre administration to both post administration timepoints will be analysed.
- Subjective Drug Effects (Safety outcome) [Immediately after and morning after drug administration]
The Drug Effects Questionnaire (DEQ) assesses the extent to which participants feel substance effects, feel high, like the effects, dislike the effects, and want more of the substance, on self-rating 100mm visual analogue scales. Change from pre administration to both post administration timepoints will be analysed.
- Postural sway (Safety outcome) [Immediately after and morning after drug administration]
Centre-of-pressure (COP) during computerised static posturography. Change from pre administration to both post administration timepoints will be analysed.
- Behavioural Alertness and Reaction Time (Safety outcome) [Morning after drug administration]
Psychomotor Vigilance Test (PVT) will be measured twice the next day, and both will be simultaneously analysed in the same mixed model scores are computed using reciprocal of the mean reaction time in milliseconds.
- Overnight Declarative Memory Consolidation (Safety outcome) [Morning after drug administration]
Word pair recall scores measured using the Computerised Word Pairs Task (WPT). Successful words recalled will be analysed.
- Overnight Procedural Memory Consolidation (Safety outcome) [Morning after drug administration]
Motor skill learning measured using the computerised Finger Tapping Task (FTT). Time in milli seconds for completion and correct sequences ("M") will be analysed.
- Resting Wake Electroencephalography (EEG) Power After Sleep (Post-Wake Effects) (Safety Outcome) [Morning after drug administration]
Resting wake EEG power during the Karolinska Drowsiness Test (KDT) upon wake: delta (1-4.5Hz), theta (4.5-8Hz), alpha (8-12Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40Hz) frequency ranges. Power spectral analysis will be applied to EEG signals from polysomnography, after artefacts are detected and removed.
- Subjective sleepiness [Assessed during each treatment arm]
The Karolinska Sleepiness Scale (KSS) is a 10-item measure of subjective drowsiness. Participants respond to each item using 9-point Likert scales ranging from 1 (Extremely alert) to 9 (Extremely sleepy). Higher scores are indicative of higher drowsiness. The KSS will be collected in accordance with Karolinska Drowsiness Test (KDT) protocol but will not be analysed due to insufficient statistical power.
- Plasma cannabinoid concentrations (Exploratory outcome) [Immediately after and morning after drug administration]
Blood collection will occur pre drug administration and after wake through each overnight treatment session.
- Urinary cannabinoid concentrations (Exploratory outcome) [Immediately after and morning after drug administration]
Urine collection will occur pre and post drug administration and twice after wake through each overnight treatment session.
- Plasma endocannabinoid concentrations (Exploratory outcome) [Immediately after and morning after drug administration]
Blood collection will occur pre drug administration and after wake through each overnight treatment session
- Urinary endocannabinoid concentrations (Exploratory outcome) [Immediately after and morning after drug administration]
Urine collection will occur pre and post drug administration and twice after wake through each overnight treatment session.
- Resting Wake Electroencephalography (EEG) Power Before Sleep (Acute Effects) (Exploratory outcome) [Immediately after drug administration]
Resting wake EEG power during the Karolinska Drowsiness Test (KDT) prior to sleep: delta (1-4.5Hz), theta (4.5-8Hz), alpha (8-12Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40Hz) frequency ranges. Power spectral analysis will be applied to EEG signals from polysomnography, after artefacts are detected and removed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males and females aged between 25-65 years;
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Insomnia Severity Index (ISI) score ≥15;
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Insomnia symptoms for more than 3-times per week for ≥3-months as determined by the medical officer;
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Ability to take oral medication;
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Provision of signed and dated informed consent form; and
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Stated willingness to comply with all study procedures and availability for the duration of the study.
Exclusion Criteria:
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Medical condition or medication that is the cause of the insomnia as determined by the medical officer;
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Known hypersensitivity to cannabis or cannabinoid products;
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Reported use of cannabis within the past 3 months as confirmed by at least one negative urine drug screen (UDS) (or at the medical officer's discretion);
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Sleep apnea (defined as Apnea Hypopnea Index [AHI] >15 and Oxygen Desaturation Index [ODI]>10) as confirmed at screening;
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Sleep-related movement disorder as determined by the medical officer;
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Delayed or advanced sleep phase syndrome (based on actigraphy and sleep diary) as confirmed screening;
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Any medical condition that produces an abnormal EEG (i.e. epilepsy, brain injury);
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Clinically relevant cardiovascular abnormalities as determined by the medical officer and a 12-lead electrocardiogram (ECG) at screening;
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Shift-work or transmeridian travel (two time zones) over last month;
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History of major psychiatric disorder in the past 12 months at the medical officer's discretion, except clinically managed mild depression and/or anxiety;
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History of suicide attempt or current suicide ideation (score greater than 1 on Q9 of the Patient Health Questionnaire [PHQ-9]);
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Pregnancy or lactating. All female volunteers will be required to complete a urine pregnancy test at screening and instructed to use a reliable form of contraception while participating in the project;
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History of drug or alcohol dependency or abuse within approximately the past 2 years;
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Use of CNS-active drugs (cannabis, amphetamines, cocaine, antidepressants, opioids, benzodiazepines) in the past 3 months as confirmed by a positive urine drug test at screening or at the medical officer's discretion;
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Use of medications that may have a clinically significant impact upon the metabolism and excretion of cannabinoids as determined by the medical officer (e.g. CYP450 enzyme inducers/inhibitors);
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Excessive caffeine use that in the opinion of the medical officer contributes to the participant's insomnia, or the inability to abstain from caffeine use 24 hours prior to each overnight sleep study;
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Inability to refrain from alcohol consumption 24 hours prior to each overnight sleep study;
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Individuals with nicotine dependence (i.e., daily smokers);
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Medical conditions that result in frequent need to get out of bed (e.g. sleep walking, nocturia);
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Psychological or behavioural treatment for insomnia, including cognitive behavioural therapy for insomnia, within 3 months before screening (excluding sleep hygiene advice);
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Occupational or judicially ordered drug alcohol screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Woolcock Institute of Medical Research | Glebe | New South Wales | Australia | 2095 |
Sponsors and Collaborators
- Woolcock Institute of Medical Research
- University of Sydney
Investigators
- Principal Investigator: Camilla Hoyos, MPH, PhD, Woolcock Institute of Medical Research
- Principal Investigator: Brendon Yee, MBChB, FRACP, FCCP, PhD, Woolcock Institute of Medical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 112/2021-08-907