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Trial registered on ANZCTR


Registration number
ACTRN12620000070932
Ethics application status
Approved
Date submitted
7/01/2020
Date registered
29/01/2020
Date last updated
20/03/2020
Date data sharing statement initially provided
29/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Cannabidiol (CBD) treatment for insomnia
Scientific title
Cannabidiol (CBD) treatment for insomnia: a three-week randomised controlled pilot trial with a placebo run-in period (CBD-INS).
Secondary ID [1] 300186 0
None
Universal Trial Number (UTN)
U1111-1246-0810
Trial acronym
CBD-INS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
insomnia 315731 0
Condition category
Condition code
Neurological 314020 314020 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This three-week, between-subjects, randomised, placebo-controlled pilot trial with a one week placebo run-in period [nightly administration of 2ml placebo (corn oil) for one week] to determine effects of a single dose of an oral cannabinoid medicine to be self-administered at least one hour before bedtime, on sleep and next-day function relative to placebo in individuals with self-reported moderate-severe insomnia [determined using a cut-off of at least 15 on the Insomnia Severity Index (ISI)] and self-reported sleep problems [self-report difficulties falling and/or staying asleep, dissatisfaction with current sleep patterns and sleep problems interfering with daily life (all yes).

The investigational product is an oral solution containing cannabinoids and corn oil at a concentration of 100mg CBD/mL. The total active treatment to be provided per day is 200mg CBD in 2mL treatment. The treatment will be self-administered one hour before bedtime. Participants will first compete a single-blind, placebo run-in period for one-week, which will involve nightly administration of 2ml placebo (corn oil) for one week. Following the placebo run-in period, treatment adherence and compliance with study protocol will be monitored by the study physician to examine for i.) non compliance (missing >20% of the treatment doses), ii.) using excessive amounts of the placebo (greater than 20ml used), or are missing >20% days wearing the GENEActiv wrist-mounted activity monitor over the one-week period (if allocated). If participants meet compliance requirements, they will be randomised into the treatment or placebo arm for the two-week period.

They will then be randomised to receive either the intervention (a single fixed dose of CBD product) or matched placebo - both 2mL/day, for an additional duration of two weeks (three weeks dosing period in total). The study investigator will instruct and coach the participant to self-administer the dose of the oral solution via a plastic syringe, to be consumed at home each night before bed (2ml/day), using a 2mL syringe provided by the study medical doctor.
Intervention code [1] 316464 0
Treatment: Drugs
Comparator / control treatment
Placebo contains the same excipient (Corn oil) as the investigational product but does not contain cannabinoids.
Control group
Placebo

Outcomes
Primary outcome [1] 322429 0
Change in insomnia severity score (ISI)
Timepoint [1] 322429 0
Assessed at two weeks after the active dosing period (comparison between CBD and placebo)(comparison between CBD versus placebo)
Primary outcome [2] 322430 0
Change in subjective sleep latency (time taken to fall asleep)
Timepoint [2] 322430 0
Assessed each day for the two week active dosing period (comparison between CBD and placebo) using a standardised self-reported questionairre (consensus sleep diary)
Primary outcome [3] 322431 0
Change in self-reported sleep efficiency (%)
Timepoint [3] 322431 0
Assessed each day for the two week active dosing period (comparison between CBD and placebo) using a standardised self-reported questionairre (consensus sleep diary)
Secondary outcome [1] 378497 0
(Primary Outcome).
Change in Wake After Sleep Onset (WASO)
Timepoint [1] 378497 0
Assessed each day for the two week active dosing period (comparison between CBD and placebo) using a standardised self-reported questionairre (consensus sleep diary)
Secondary outcome [2] 378498 0
Subjective ratings of changes in sleep-wake behaviour on the Leeds Sleep Evaluation Questionnaire (LSEQ)
Timepoint [2] 378498 0
Assessed at day 7 (following placebo-run in period), at day 14 and at day 21 of the active dosing period.
Secondary outcome [3] 378499 0
Subjective ratings of changes in sleep-wake behaviour on the Glasgow Sleep Effort Scale (GSES)
Timepoint [3] 378499 0
Assessed at day 7 (following placebo-run in period), at day 14 and at day 21 of the active dosing period.
Secondary outcome [4] 378500 0
Subjective ratings of alertness using a visual analogue scale (VAS)
Timepoint [4] 378500 0
Each day during the dosing period (three weeks)
Secondary outcome [5] 378501 0
Subjective medicine effects (Nausea (or vomiting, Dizziness, Irritability, dry mouth, light headedness, diarrhoea) using a check-box and qualitative question-answer (designed specifically for this study)
Timepoint [5] 378501 0
Each day during the dosing period (three weeks)
Secondary outcome [6] 378502 0
Elapsed sleep time (mins) from wrist-mounted Actigraphy watch
Timepoint [6] 378502 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [7] 378503 0
Sleep time (mins) from wrist-mounted Actigraphy watch
Timepoint [7] 378503 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [8] 378504 0
Sleep efficiency (%) from wrist-mounted Actigraphy watch
Timepoint [8] 378504 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [9] 378505 0
number of activity periods from wrist-mounted Actigraphy watch
Timepoint [9] 378505 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [10] 378506 0
Median activity period (mins) from wrist-mounted Actigraphy watch
Timepoint [10] 378506 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [11] 378507 0
Previous day total energy (MET mins) from wrist-mounted Actigraphy watch
Timepoint [11] 378507 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [12] 378508 0
Previous day total light exposure (Lux mins) from wrist-mounted Actigraphy watch
Timepoint [12] 378508 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [13] 378509 0
body temperature (degrees) from wrist-mounted Actigraphy watch
Timepoint [13] 378509 0
Assessed continuously throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [14] 378510 0
bed time from wrist-mounted Actigraphy watch
Timepoint [14] 378510 0
Assessed each day throughout three week dosing period (comparison between CBD versus placebo)
Secondary outcome [15] 378511 0
rise time from wrist-mounted Actigraphy watch
Timepoint [15] 378511 0
Assessed each day throughout three week dosing period (comparison between CBD versus placebo)

Eligibility
Key inclusion criteria
1. Males and Females Aged 18-45 years
2. Insomnia Severity Index (ISI) score of 15 or more.
3. Self-report difficulties falling and / or staying asleep (yes)
4. Dissatisfaction with current sleep patterns (yes)
5. Sleep problems interfering with daily life (yes)
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to speak or read English
2. Current shift worker
3. History of severe neurological, cardiac, endocrine, gastrointestinal, or bleeding disorders (self-report)
4. History of major psychiatric disorder in the past 12 months except clinically-managed mild depression
5. Severe current depression (BDI score of greater than or equal to 20)
6. Severe current anxiety (BAI score greater than or equal to 16)
7. 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.
8. Use of any CNS-active drugs (including antidepressants, opioids, benzodiazepines) for the past 3 months or at the medical officer’s discretion
9. Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia
10. Other pre-existing sleep disorder (restless legs syndrome, narcolepsy, parasomnias etc.) (self-report)
11. Used any modality of treatment for insomnia, including CBT, within 3 months before screening or at the medical doctor's discretion
12. History of drug or alcohol dependency or abuse within approximately the past 2 years (self-report and at medical officer’s discretion)
13. Probable moderate to severe obstructive sleep apnoea (STOP-BANG questionnaire)
14. Currently participating in any other trials involving investigational or marketed products within 30 days prior to the screening visit.
15. Not willing to abstain from driving, riding, operating heavy machinery for 8 hours after taking the nightly treatment.

The following interim exclusion criteria will occur on conclusion of the one-week placebo-run in period and prior to randomisation into the treatment arms (CBD vs placebo).
1. Placebo responder. Placebo responders will be identified and eliminated from the trial before randomisation. A placebo responder will be defined as any person entering the trial who significantly changes their subjective sleep scores derived from the sleep diary during the 7-day placebo run-in. This will be operationally defined as an individual whose:
o Subjective Sleep Efficiency (SE) goes above 85%
o Subjective Sleep Onset Latency (SOL) goes below 31 minutes
o Subjective Wake after Sleep Onset (WASO) goes below 31 minutes, as determined by the Subjective sleep information questions.

2. Non-compliers. Non-compliers will be identified as those;
a. Missing greater than or equal to 20% of the treatment doses
b. Using excessive amounts of the treatment (placebo) (greater than 20ml used).
c. Missing greater than or equal to 20% days wearing the GENEActiv wrist-mounted activity monitor over the one-week run-in period (if assigned).

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, all eligible participants will first be provided with a one-week supple of placebo oil (single blinded). Eligibility to compete the two week dosing period will be reconfirmed according to the interim exclusion criteria for placebo-repsonders (see exclusion criteria). Once eligibility has been reconfirmed, participants be randomly allocated to treatment (active vs placebo). 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 participant.
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
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range). The number and percentage of subjects will be presented for categorical variables.
All statistical tests will be performed two tailed at the 5% significance level and performed using IBM SPSS statistical package. Z scores for the distribution will be calculated for each variable and displayed in histogram form. Out of range values will be recoded as missing values.

Separate linear mixed effect (LME) models with Maximum Likelihood (ML) estimation will be applied to assess differences in sleep and other outcomes over time. Post hoc comparisons will be undertaken where significant condition or interaction effects are observed to determine the significance of differences between groups as a function of treatment group.

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)
VIC

Funding & Sponsors
Funding source category [1] 304619 0
Charities/Societies/Foundations
Name [1] 304619 0
Barbara Dicker Brain Sciences Foundation (BDBSF)
Address [1] 304619 0
John St, Hawthorn VIC 3122
Country [1] 304619 0
Australia
Primary sponsor type
University
Name
Swinburne University of Technology
Address
John St, Hawthorn VIC 3122
Country
Australia
Secondary sponsor category [1] 304914 0
None
Name [1] 304914 0
none
Address [1] 304914 0
none
Country [1] 304914 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305040 0
Swinburne University Human Research Ethics
Ethics committee address [1] 305040 0
Research Ethics Officer,
Swinburne Research (H68),
Swinburne University of Technology,
P O Box 218,
Hawthorn, Victoria, 3122.
Ethics committee country [1] 305040 0
Australia
Date submitted for ethics approval [1] 305040 0
07/02/2020
Approval date [1] 305040 0
18/03/2020
Ethics approval number [1] 305040 0
20202751-4005

Summary
Brief summary
Insomnia is a highly prevalent and burdensome disease. It is thought to affect as many as one in three adults worldwide at any one time. Treatment options for insomnia are often limited to doctor-implemented cognitive behavioural training (CBT), pharmaceutical intervention, or a combination of the two. Whilst traditionally effective, both options have considerable limitations, most frequently those associated with cost, compliance and effectiveness (CBT), or tolerance and addiction potential (pharmaceutical).

The Australian Federal Government recently approved the medical use of cannabinoids among select patient groups. The main active ingredient, cannabidiol (CBD), may have sedating and/or sleep-enhancing effects. There is therefore increasing global interest as its potential use as an alternate sleep-aid.

The primary objective of this research is to examine whether 2 weeks of nightly supplementation with a novel sublingual CBD-treatment improves sleep outcomes among individuals with moderate-severe insomnia. Specifically, we seek to examine the effect of treatment on subjective [sleep onset latency, sleep efficiency (%), and time awake after sleep onset] and objective sleep quality [as measured by Actigraphy outcomes (time in bed, sleep efficiency (%), number of awakenings, sleep latency) after 2-week supplementation with sublingual CBD compared with a placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99070 0
Dr Amie Hayley
Address 99070 0
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 99070 0
Australia
Phone 99070 0
+61 3 92145585
Fax 99070 0
Email 99070 0
ahayley@swin.edu.au
Contact person for public queries
Name 99071 0
Dr Amie Hayley
Address 99071 0
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 99071 0
Australia
Phone 99071 0
+61 3 92145585
Fax 99071 0
Email 99071 0
ahayley@swin.edu.au
Contact person for scientific queries
Name 99072 0
Dr Amie Hayley
Address 99072 0
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
Mail H24
PO Box 218
Hawthorn, Victoria, 3122
Country 99072 0
Australia
Phone 99072 0
+61 3 92145585
Fax 99072 0
Email 99072 0
ahayley@swin.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
It is expected that the results of this trial will be disseminated via peer-reviewed publications and at academic conferences. For these purposes the data will be collated and analysed as group data.
What supporting documents are/will be available?
No other documents available
Summary results
No Results