Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000632897
Ethics application status
Approved
Date submitted
26/03/2021
Date registered
27/05/2021
Date last updated
28/02/2023
Date data sharing statement initially provided
27/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase III Double-Blind, Randomised Placebo-Controlled Clinical Trial to evaluate the efficacy and safety of a botanical cannabidiol (CBD) for sleep disturbances in a healthy population.
Scientific title
A Phase III Double-Blind, Randomised Placebo-Controlled Clinical Trial to evaluate the efficacy and safety of a botanical CBD for sleep disturbances in a healthy population via the PROMIS sleep disturbance instrument.
Secondary ID [1] 303750 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
CANN-Sleep
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep Disturbances 321235 0
Anxiety 321236 0
chronic pain 321245 0
Fatigue 321246 0
Condition category
Condition code
Alternative and Complementary Medicine 319025 319025 0 0
Herbal remedies
Mental Health 319483 319483 0 0
Anxiety
Mental Health 319484 319484 0 0
Other mental health disorders
Neurological 319485 319485 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will involve a 15mg CBD per soft gelatin capsule. The active product will contain hemp seed oil as the carrier and 0.5 mL of liquid encapsulated into a gelatin/ glycerin soft capsule. CBD will make up >98% of the total cannabinoids in the capsule. Non-active ingredients include hemp seed oil, glycerin and gelatin. The product will be packaged into white, opaque HDPE pill packer bottles with a 0.5 g desiccant and a white, heat-induction cap and perforated neckband. The product will be labelled with the identity of the group. Full list of ingredients used: Cold-Press Hemp Seed Oil and Hemp THC-Free Broad-spectrum extract, Glycerin and Gelatin.

Initially, participants will undergo a titration period of two weeks. During this time, they will be taking 1 capsule after breakfast and 1 capsule 30 minutes before bed. The second day, the participant will take 2 capsules after breakfast and before bed. If 2 capsules made the person drowsy through the day, it will be reduced to 1 capsule. The night dose will continue to increase by 1 capsule each night until the participant feels that is best dose to help their sleep or they reach maximum dose. Maximum dose during the titration period will be maximum morning dose being 2 capsules and the maximum night dose being 8-9 capsules (10 capsules per day).

After the titration period, the participants will stay on their maximum dose for 8 weeks or until they withdraw from the study. In total, the study should be 10 weeks in total with a one month follow up phone call after ceasing the medication.

Compliance will be measured by capsule return and counting at each follow-up. The participants will be asked to bring back all empty containers as well as those with capsules remaining. These will also be checked against the participant diaries.
Intervention code [1] 320069 0
Treatment: Other
Intervention code [2] 320415 0
Treatment: Drugs
Comparator / control treatment
The control treatment will be the placebo group. The placebo group will be given 15mg capsules to be taken with the same instructions as the active group. The capsule itself with be similar in appearance, taste and smell to the active group. The oil that will be used as the placebo is medium chain triglyceride (MCT) oil. in a glycerin/gelatin soft cell capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 326931 0
To evaluate the efficacy of a botanical CBD for sleep disturbances compared to a placebo via the PROMIS sleep disturbance instrument.
Timepoint [1] 326931 0
At the enrolment/ baseline visit (week -2) and week 4 and week 8 (primary endpoint) post-randomisation.
Secondary outcome [1] 393163 0
To evaluate the efficacy of CBD for anxiety comparing botanical CBD versus placebo via the Hamilton Anxiety Rating Scale.
Timepoint [1] 393163 0
At the enrolment/ baseline (week -2) and week 4 and week 8 post-randomisation.
Secondary outcome [2] 393164 0
To evaluate the efficacy of CBD for chronic pain (as defined as greater than 3 months of chronic pain) comparing botanical CBD versus placebo via the pain disability index (PDI).
Timepoint [2] 393164 0
At the enrolment/ baseline (week -2) and week 4 and week 8 post-randomisation.
Secondary outcome [3] 393165 0
To assess the quality of life of CBD comparing botanical CBD versus placebo via the SF-20.
Timepoint [3] 393165 0
At the enrolment/ baseline visit (week -2) and week 4 and week 8 post-randomisation.
Secondary outcome [4] 393166 0
To assess quality of life of CBD comparing botanical CBD versus placebo via the Brief Fatigue inventory
Timepoint [4] 393166 0
Once a week for 8 weeks post-randomisation visit. Each time point will be evaluated using a longitudal analysis.
Secondary outcome [5] 393167 0
To assess safety of CBD via side effect profile via direct observation on follow up phone calls and face to face visits and participant reported on participant diaries.
Timepoint [5] 393167 0
At the enrolment/baseline visit (week -2) and week 4 and week 8 (end point) post-randomisation.
Secondary outcome [6] 393168 0
To assess liver enzymes for safety via pathology testing.
Timepoint [6] 393168 0
At the enrolment/ baseline (week -2) and week 4 and week 8 (end point) post-randomisation.
Secondary outcome [7] 394734 0
Assessing the number and severity of adverse events via CTCAE.
Timepoint [7] 394734 0
At the enrolment/baseline visit (week -2) and week 4 and week 8 (end point) post-randomisation.
Secondary outcome [8] 394735 0
To assess kidney function via blood pathology.
Timepoint [8] 394735 0
At the enrolment/baseline visit (week -2) and week 4 and week 8 (end point) post-randomisation.

Eligibility
Key inclusion criteria
1. Adults aged between 18 and 65 years old.
2. Considered to be generally healthy.
3. A self-reported complaint of poor sleep quality that includes one or more of the following:
-Difficulty initiating sleep
-Difficulty maintaining sleep
-Waking up earlier than desired
4. Self-reports sleep difficulty occurring three nights a week or more for three months.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or breast-feeding women
2. Anyone with an acute disease
3. Severe sleep disturbances
4. Current sleep apnoea (historical diagnosis of sleep apnoea which has since resolved is acceptable)
5. Diagnosed sleep disturbances (e.g. narcolepsy, parasomnias, insomnias)
6. Severe anxiety
7. Current, clinically significant anxiety disorder
8. History of an unmanaged and/or poorly managed chronic disease
9. Severe mental illness, suicidal ideation and/or difficulty communicating (mild to moderate, well-managed depression is acceptable)
10. Current antipsychotic use
11. Recreational drug use (positive DOA urine test). If screening DOA test is positive to THC ONLY, participants will have the opportunity for 1 x re-test 2 weeks after the positive result.
12. Alcohol intake higher than 14 units per week
13. Smokes more than 2 nicotine cigarettes daily
14. Works regular shift work
15. Travels across more than 2 time zones in the last two weeks.
16. Consumes more than 300mg/day of caffeine. (The average cup of coffee is equivalent to 95-100mg of caffeine so 300mg is equivalent to 3 cups of coffee, 4 cups of regular tea and 6 of 350ml of cola. It is advised that no caffeine be consumed after 3pm in the afternoon.)
17. People with liver enzymes greater than 1.5 x ULN (a single re-test of screening pathology is permitted)
18. People who have ever had a cardiac arrest or have current clinically significant cardiovascular disease
19. eGFR < 60
20. Any elevation in creatinine on screening pathology above the ULN
21. Current oral steroid administration (concurrent use of topical and/or inhaled steroids are acceptable)
22. Current chemotherapy, radiation, immune suppressant therapy, immunotherapy or similar medical treatments.
23. Current warfarin administration
24. Current amphetamine administration (prescription or illicit) (e.g. Ritalin, Adderall, Concerta)
25. Presence of implanted electronic medical device (e.g. pacemaker, defibrillator)
26. Vaccination of any kind in the 14 days prior to commencing IMP administration,

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)
All researchers will be blinded to the randomization and the allocation. A computer-generated randomized group allocation (A and B)will be provided by the computer system. The number is concealed until the RA enrolls the participant into the data management system. The number will then appear on the participants file. The participants will be allocated to one of two groups and the group allocation will be noted on the computer system data management and the participant hard copy chart.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation sequence will be a computer-generated random number based on stratified block randomisation. Strata will be based on trial site. Blocks will be of varying sizes ranging from 6 to 12. The numbers will be generated via https://www.randomizer.org/.
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 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All data will be analysed via SPSS 25.0. Analyses will be conducted on an intention-to-treat basis with per-protocol subgroup analysis based on anxiety and chronic pain. Descriptive statistics will summarise data as either means (absolute, relative or percentage change) with standard deviations or medians with interquartile range as appropriate for the data. The safety data will be summarised via descriptive statistics. The primary outcome PROMIS sleep disturbance questionnaire after 8 weeks at full titration will be compared between groups using univariate analysis (ANCOVA) or equivalent non-parametric test depending on the distribution of data, and the effects reported as group differences with 95% confidence intervals. The responder rate will be compared using Chi2 tests. Secondary outcomes will be analysed using comparable methods depending on the data type.
The subject population for analysis will be classified as: Protocol-compliant population. This means all participants randomised into the study that received the protocol required study product (administered at least 90% each week) exposure for at least one month.
End of trial analysis plan:
1. Scores of the PROMIS sleep disturbance between botanical CBD and placebo: Scores of the PROMIS sleep questionnaire will be compared via ANCOVA and/or a two-sample t-test. Or equivalent non-parametric test depending on data
2. Scores of the Hamilton Anxiety Rating Scale (HAM-A) sleep disturbance between botanical CBD and placebo: Scores of the HAM-A will be compared via ANCOVA and/or a two-sample t-test. Or equivalent non-parametric test depending on data
3. Scores of the Pain Disability Index (PDI) sleep disturbance between botanical CBD and placebo: Scores of the PDI will be compared via ANCOVA and/or a two-sample t-test. Or equivalent non-parametric test depending on data
4. Scores of the Brief Fatigue Index (BFI) sleep disturbance between botanical CBD and placebo: Scores of the BFI will be compared via ANCOVA and/or a two-sample t-test. Or equivalent non-parametric test depending on data
5. Scores of the short form-20 (SF-20) sleep disturbance between botanical CBD and placebo: Scores of the SF-20 will be compared via ANCOVA and/or a two-sample t-test. Or equivalent non-parametric test depending on data
6. Scores of the blood pathology markers: Blood pathology changes will be compared using paired T tests and longitudinal analysis (GEE) between the intervention groups and placebo.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/06/2021
Actual
1/09/2021
Date of last participant enrolment
Anticipated
5/05/2022
Actual
7/09/2022
Date of last data collection
Anticipated
26/09/2022
Actual
16/11/2022
Sample size
Target
438
Accrual to date
Final
328
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment postcode(s) [1] 33494 0
2480 - Lismore
Recruitment postcode(s) [2] 33495 0
4000 - Brisbane
Recruitment postcode(s) [3] 33496 0
2000 - Sydney
Recruitment postcode(s) [4] 33497 0
3000 - Melbourne
Recruitment postcode(s) [5] 33498 0
4103 - Annerley
Recruitment postcode(s) [6] 33499 0
4217 - Gold Coast
Recruitment postcode(s) [7] 33500 0
2478 - Ballina

Funding & Sponsors
Funding source category [1] 308157 0
Commercial sector/Industry
Name [1] 308157 0
EcoFibre
Country [1] 308157 0
Australia
Primary sponsor type
University
Name
Southern Cross University
Address
1 Military Road, East Lismore NSW 2480 Australia
Country
Australia
Secondary sponsor category [1] 308933 0
None
Name [1] 308933 0
None
Address [1] 308933 0
None
Country [1] 308933 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308142 0
Southern Cross University Human Research Ethics Committee
Ethics committee address [1] 308142 0
Ethics committee country [1] 308142 0
Australia
Date submitted for ethics approval [1] 308142 0
15/03/2021
Approval date [1] 308142 0
13/04/2021
Ethics approval number [1] 308142 0
SCU HREC 2021/031

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109682 0
Dr Janet Schloss
Address 109682 0
National Centre for Naturopathic Medicine
Southern Cross University
1 Military Road,
Lismore NSW 2480
Country 109682 0
Australia
Phone 109682 0
+61 0436 101 306
Fax 109682 0
Email 109682 0
[email protected]
Contact person for public queries
Name 109683 0
Janet Schloss
Address 109683 0
National Centre for Naturopathic Medicine
Southern Cross University
1 Military Road,
Lismore NSW 2480
Country 109683 0
Australia
Phone 109683 0
+61 0436 101 306
Fax 109683 0
Email 109683 0
[email protected]
Contact person for scientific queries
Name 109684 0
Janet Schloss
Address 109684 0
National Centre for Naturopathic Medicine
Southern Cross University
1 Military Road,
Lismore NSW 2480
Country 109684 0
Australia
Phone 109684 0
+61 0436 101 306
Fax 109684 0
Email 109684 0
[email protected]

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 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.