Cannabinol Use in Patients With Insomnia Disorder (CUPID)

February 5, 2024 updated by: Woolcock Institute of Medical Research

A Randomised, Double-blind, Placebo-controlled, Single-dose, Crossover, Pilot Study Investigating the Effects of Cannabinol (CBN) 30 mg and 300 mg on Sleep Architecture and Next-day Function in Insomnia Disorder

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Glebe, New South Wales, Australia, 2095
        • Woolcock Institute of Medical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Between 25 - 65 years of age
  2. Insomnia Severity Index (ISI) score ≥ 15 at eligibility screening
  3. Insomnia disorder (symptoms occurring at least 3 times per week and present for longer than 3 months) as determined by the study physician
  4. Ability to take oral medication
  5. Provision of signed and dated informed consent form
  6. Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

  1. Medical condition or medication that is the cause of the insomnia disorder as determined by the study physician
  2. Known hypersensitivity to cannabis or cannabinoid products (including if this becomes evident during the trial)
  3. Reported use of cannabis or cannabinoid products within the past 3 months as confirmed by at least one negative urine drug screen (UDS) (or at the study physician's discretion)
  4. Sleep apnoea (defined as Apnoea Hypopnea Index [AHI] > 15 and Oxygen Desaturation Index [ODI]>10) as confirmed by polysomnography at screening
  5. Sleep-related movement disorder as determined by the study physician
  6. Delayed or advanced sleep phase syndrome (based on actigraphy and sleep diary) as confirmed during screening
  7. Any medical condition that produces an abnormal EEG (i.e., epilepsy, brain injury)
  8. Clinically relevant cardiovascular abnormalities as determined by the study physician and a 12-lead electrocardiogram (ECG) at screening
  9. Shift work or trans meridian travel (two time zones) within the last month
  10. History of major psychiatric disorder in the past 12 months at the study physician's discretion, except clinically managed mild depression and/or anxiety
  11. History of suicide attempt or current suicide ideation (score greater than 1 on Q9 of the Patient Health Questionnaire [PHQ-9])
  12. Pregnancy or lactating. Female participants are required to complete a urine pregnancy test at screening and treatment sessions and all participants are instructed to use a reliable form of contraception throughout the study duration
  13. History of drug or alcohol dependency or abuse within approximately the past 2 years
  14. 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 study physician's discretion
  15. Use of medications that may have a clinically significant impact upon the metabolism and excretion of cannabinoids as determined by the study physician (e.g., CYP450 enzyme inducers/inhibitors
  16. Excessive caffeine use that in the opinion of the study physician contributes to the participant's insomnia disorder, or the inability to abstain from caffeine use 24 hours prior to each overnight sleep study
  17. Inability to refrain from alcohol consumption 24 hours prior to each overnight sleep study
  18. Individuals with nicotine dependence (i.e., daily smokers)
  19. Medical conditions that result in frequent need to get out of bed (e.g., sleep walking, nocturia)
  20. Psychological or behavioural treatment for insomnia disorder, including cognitive behavioural therapy for insomnia, within 3 months before screening (excluding sleep hygiene advice)
  21. Occupational or judicially ordered drug screening
  22. Has held an unrestricted driving license < 1 year
  23. Cannot speak English fluently

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:
  • ECS 310 (1.5%)
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:
  • ECS 310 (15%)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Wake After Sleep Onset (WASO)
Time Frame: Night 1
WASO measured in minutes using in-laboratory overnight polysomnography, from the first epoch after lights out until the last epoch, scored as any stage of sleep by an experienced polysomnographic technician in accordance with American Academy of Sleep Medicine (AASM) 2020 Sleep Scoring criteria (Version 2.6). Comparisons between each CBN dose versus placebo.
Night 1

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Traditional sleep staging
Time Frame: Night 1
Proportion of the sleep opportunity scored at the 5 stages (wake, and N1, N2, N3, and REM sleep) between lights out and lights on, measured using overnight in-laboratory polysomnography, scored by a polysomnography technician in accordance with AASM Sleep Scoring criteria. Comparisons between each CBN dose versus placebo.
Night 1
Sleep Onset Latency (SOL)
Time Frame: Night 1
SOL measured in minutes using in-laboratory polysomnography, calculated from the time of lights out to the first sleep epoch as scored by a polysomnographic technician in accordance with AASM Sleep Scoring criteria. Comparisons between each CBN dose versus placebo.
Night 1
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep.
Time Frame: Night 1
Spectral power of delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography after artefacts are detected and removed. Comparisons between each CBN dose versus placebo.
Night 1

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sleep Spindles During Non-Rapid Eye Movement (NREM) Sleep (Tertiary outcome)
Time Frame: Night 1
Sleep spindle and slow oscillation events in NREM sleep from in-laboratory overnight polysomnography. A sleep spindle and slow oscillation detection algorithm will be applied to electroencephalography (EEG) signals from polysomnography after artefacts are detected and removed. Comparisons between each CBN dose versus placebo.
Night 1
Electroencephalogram (EEG) Arousal Index (Tertiary outcome)
Time Frame: 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. Comparisons between each CBN dose versus placebo.
Night 1
Absolute Electroencephalography (EEG) Power During Rapid Eye Movement (REM) Sleep (Tertiary outcome)
Time Frame: Night 1
Spectral power of delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography after artefacts are detected and removed. Comparisons between each CBN dose versus placebo.
Night 1
Next day post-wake subjective sleep evaluation (LSEQ) (Tertiary outcome)
Time Frame: Morning after drug administration
LSEQ score. LSEQ scores range from 0-100, with higher scores indicating better subjective experience. Assessed within 1 h after wake (comparison between each CBN dose versus placebo).
Morning after drug administration
Next day post-wake subjective sleep evaluation (RCSQ) (Tertiary outcome)
Time Frame: Morning after drug administration
RCSQ score. RCSQ scores range from 0-100, with higher scores indicating better subjective experience. Assessed within 1 h after wake (comparison between each CBN dose versus placebo).
Morning after drug administration
Standard Deviation of Lateral Position (SDLP) During Next-day Post-Wake Simulated Drive (Safety outcome)
Time Frame: Morning after drug administration
SDLP ("weaving") is measured across the 'standard', 'car following', and 'divided attention' sub-sections of a ~30 minute simulated driving task. Assessed within 2 h after wake (comparison between each CBN dose versus placebo).
Morning after drug administration
Speed During Next-day Post-Wake Simulated Drive (Safety outcome)
Time Frame: Morning after drug administration
Average speed and standard deviation of speed is measured across the 'standard' and 'divided attention' sub-sections of a ~30 minute simulated driving task. Assessed within 2 h after wake (comparison between each CBN dose versus placebo).
Morning after drug administration
Distance Headway During Next-day Post-Wake Simulated Drive (Safety outcome)
Time Frame: Morning after drug administration
Average distance headway (i.e., distance between the driver's vehicle and vehicle immediately in front) and standard deviation of distance headway is measured across the 'car following' sub-section of a ~30-minute simulated driving task. Assessed within 2 h after wake at both treatment sessions (comparison between each CBN dose versus placebo).
Morning after drug administration
Subjective Mood Evaluation (Safety outcome)
Time Frame: Immediately after and morning after drug administration
The Abbreviated Profile of Mood States (POMS) consists of 40 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). A total mood disturbance score is calculated by summing negative domains and subtracting positive domains. Administered pre and post drug administration, as well as next-day (comparison between each CBN dose versus placebo).
Immediately after and morning after drug administration
Subjective Drug Effects (Safety outcome)
Time Frame: Immediately after and morning after drug administration
The Drug Effects Questionnaire (DEQ) assesses the extent to which participants feel a drug effects, feel high, like the effects, dislike the effects, want more of the substance, and feel sedated, on self-rating 100mm visual analogue scales. A total mood disturbance score is calculated by summing negative domains and subtracting positive domains. Administered pre and post drug administration, as well as next-day (comparison between each CBN dose versus placebo).
Immediately after and morning after drug administration
Postural sway (Safety outcome)
Time Frame: Immediately after and morning after drug administration
Centre-of-pressure (COP) during computerised static posturography. Administered pre and post drug administration, as well as next-day (comparison between each CBN dose versus placebo).
Immediately after and morning after drug administration
Behavioural Alertness and Reaction Time (Safety outcome)
Time Frame: Morning after drug administration
Psychomotor Vigilance Test (PVT) is administered twice the next-day (comparison between each CBN dose versus placebo).
Morning after drug administration
Overnight Declarative Memory Consolidation (Safety outcome)
Time Frame: Morning after drug administration
Word pair recall scores measured using the computerised Word Pairs Task (WPT). Administered pre-drug administration and next-day (comparison between each CBN dose versus placebo).
Morning after drug administration
Overnight Procedural Memory Consolidation (Safety outcome)
Time Frame: Morning after drug administration
Motor sequence learning measured using the computerised Finger Tapping Task (FTT). Administered pre-drug administration and next-day (comparison between each CBN dose versus placebo).
Morning after drug administration
Resting Wake Electroencephalography (EEG) Power After Sleep (Post-Wake Effects) (Safety Outcome)
Time Frame: Morning after drug administration
Resting wake EEG power during the Karolinska Drowsiness Test (KDT) upon wake: delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges. Power spectral analysis is applied to EEG signals from polysomnography, after artefacts are detected and removed. Comparison between each CBN dose versus placebo.
Morning after drug administration
Subjective sleepiness after sleep
Time Frame: Morning after drug administration
The Karolinska Sleepiness Scale (KSS) is a 10-item measure of subjective drowsiness. Participants respond to each item using a 9-point Likert scale ranging from 1 (Extremely alert) to 9 (Extremely sleepy). Higher scores are indicative of increased drowsiness. The KSS will be collected in accordance with the KDT protocol but will not be analysed due to insufficient statistical power.
Morning after drug administration
Resting Wake Electroencephalography (EEG) Power Before Sleep (Acute Effects)(Exploratory outcome)
Time Frame: Immediately after drug administration
Resting wake EEG power during the KDT prior to sleep: delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges. Power spectral analysis is applied to EEG signals from polysomnography, after artefacts are detected and removed. Comparison between each CBN dose versus placebo.
Immediately after drug administration
Subjective sleepiness after sleep (acute effects) (Exploratory outcome)
Time Frame: Immediately after drug administration
The 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 the KDT protocol but will not be analysed due to insufficient statistical power.
Immediately after drug administration
Plasma cannabinoid concentrations (Exploratory outcome)
Time Frame: Immediately after and morning after drug administration
Presence of cannabinoids (CBN, delta-9-tetrahydrocannabinol [THC], and cannabidiol [CBD]) (e.g., 11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC, 7-OH-CBD, 7-COOH-CBD), and endocannabinoids and related molecules (e.g., 2-Arachidonoylglyceroland anandamide) and their metabolites in plasma samples.
Immediately after and morning after drug administration
Urinary cannabinoid concentrations (Exploratory outcome)
Time Frame: Immediately after and morning after drug administration
Presence of cannabinoids (CBN, THC, and CBD) and their metabolites (11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC, 7-OH-CBD, 7-COOH-CBD) in urine samples.
Immediately after and morning after drug administration
Salivary cannabinoid concentrations (Exploratory outcome)
Time Frame: Immediately after and morning after drug administration
Presence of cannabinoids (THC, CBN) and their metabolites (11-OH-CBN, 11-COOH-CBN, 11-OH-THC, 11-COOH-THC) in saliva samples.
Immediately after and morning after drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Woolcock Institute of Medical Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Sydney

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 24, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 29, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 5, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 12, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 25, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 112/2021-08-907

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Non-identifiable IPD will be shared upon reasonable request to the Chief Investigators.

IPD Sharing Time Frame

Non-identifiable IPD will become available one year after the Actual Study Completion Date and will be available for 10 years.

IPD Sharing Access Criteria

Individual participant level meta-analyses of congruent studies

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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