The CANabidiol Use for RElief of Short Term Insomnia

Study Overview
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Brief Summary
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This study aims to investigate the effect of 50 mg and 100 mg per day oral CBD product versus a placebo over 8 weeks on insomnia severity in adults aged 18-65 years old with insomnia symptoms.

Detailed Description
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This is a double-blind, randomised, parallel-group, placebo-controlled study of 8 weeks of oral CBD at 50 or 100 mg per day versus placebo in 198 participants with insomnia symptoms as classified by an Insomnia Severity Index (ISI) score of 8-21. Participants will be recruited voluntarily and are able to withdraw at any time. The study will be conducted online with telehealth consults where required.

Official Title
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The CANabidiol Use for RElief of Short Term Insomnia (CAN-REST). A Randomised, Double-Blind, Placebo-Controlled Clinical Study

Conditions
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Sleep Disturbance, Insomnia, Insomnia Type; Sleep Disorder, Insomnia, Transient, Insomnia Due to Anxiety and Fear, Insomnia Due to Other Mental Disorder

Intervention / Treatment
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* Drug: 50 mg Cannabidiol (CBD)
* Drug: Placebo
* Drug: 100 mg Cannabidiol (CBD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and females aged 18-65 years old, inclusive. Females must be non-pregnant, non-lactating. Proficient in English and have internet access and a mobile phone. Insomnia symptoms as classified by an Insomnia Severity Index (ISI) score of 8 - 21 and have experienced these symptoms over the past month at pre-screening. Stated willingness to comply with all study procedures and availability for the duration of the study. Provision of signed and dated informed consent form. All male and females of childbearing potential must agree to use two forms of effective contraception from the time of signing informed consent until 30 days after study completion. Exclusion Criteria: Serious medical and/or psychiatric illnesses/disorders that will require treatment during the trial period. The use of any drug known to affect sleep during the study one week prior the randomization, including: Sedatives (benzodiazepines, Z drugs, agomelatine, suvorexant, sodium oxybate, sedating antidepressants, sedating antihistamines, antipsychotics, melatonin, valerian). Opioids (e.g. morphine, codeine, oxycodone, methadone, buprenorphine, fentanyl, tramadol, tapentadol, hydromorphone). Stimulants (e.g. methylphenidate, dexamphetamine, modafinil, phentermine). Excessive caffeine use (defined as > 600mg caffeine or approximately 6 cups of caffeinated beverages a day) that, in the opinion of the medical doctor, contributes to the participant's insomnia. Excessive alcohol use (defined as per NHMRC guideline, i.e. no more than four standard drinks per day on average for men, and for women, no more than two). The use of cannabinoids or a cannabinoid-based medicine within 3 months prior to study Day 1 and unwillingness to abstain from recreational drug use during the study period. Cannabis dependence or any other drug or alcohol dependence within the past two years. Positive urine drug screen (e.g., amphetamines type substances, benzodiazepines, cannabinoids, cocaine, and opiates) at screening or Day -1 or a history of drug abuse within the past 2 years. Known hypersensitivity to cannabis-based products or any of the excipients in the study drug. Use of any investigational drug or involvement in another clinical trial within 30 days of screening day. Use of anti-coagulant drugs such as warfarin or those known to be metabolised by CYP450 enzymes. Current or ongoing treatments for insomnia (e.g. cognitive-behavioural therapy (CBT) and CNS-active drugs). Obstructive sleep apnoea determined by the MAPI questionnaire or other self-reported sleep disorders. Medical conditions that result in frequent sleep disturbance (e.g. nocturia). History of attempted suicide in the past 12 months. Clinically significant hepatic abnormalities determined by the screening blood test. Shift work, jet lag or trans-meridian travel (two time zones) in the past month.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, placebo-controlled, double-blind, parallel trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg CBD<br>50 mg CBD to be administered as a single oral dose. Each capsule contains 25 mg CBD. Two capsules to be taken (plus two placebo capsules) | Drug: 50 mg Cannabidiol (CBD)<br>* For the study arm, '50 mg CBD' participants take two (2) CBD capsules and two (2) placebo capsules.<br>* Other names: BodECS BioAbsorb(TM) capsule;Drug: Placebo<br>* Participants take four (4) placebo capsules.<br>Drug: 100 mg Cannabidiol (CBD)<br>* For the study arm, '100 mg CBD' participants take four (4) CBD capsules.<br>* Other names: BodECS BioAbsorb(TM) capsule;|
| Experimental: 100 mg CBD<br>100 mg CBD to be administered as a single oral dose. Each capsule contains 25 mg CBD. Four capsules to be taken. | Drug: 50 mg Cannabidiol (CBD)<br>* For the study arm, '50 mg CBD' participants take two (2) CBD capsules and two (2) placebo capsules.<br>* Other names: BodECS BioAbsorb(TM) capsule;Drug: 100 mg Cannabidiol (CBD)<br>* For the study arm, '100 mg CBD' participants take four (4) CBD capsules.<br>* Other names: BodECS BioAbsorb(TM) capsule;|
| Placebo Comparator: Placebo<br>Placebo capsules contain no CBD. Four capsules to be taken as a single oral dose. | Drug: Placebo<br>* Participants take four (4) placebo capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the effect of the administration of a 50mg and 100mg per day oral CBD product versus placebo over 8 weeks on insomnia severity index scores | Insomnia Severity Index (ISI): A 7-item tool measuring the nature, severity, and impact of insomnia over the past 2 weeks. Each item uses a 5-point Likert scale to capture a rating (0 = no problem; 4 = very severe problem) which add up to: no insomnia (0 - 7); sub-threshold insomnia (8 - 14); moderate insomnia (15 - 21); and severe insomnia (22 - 28). | Baseline (week 0), week 4, week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of 8 weeks of 50mg or 100mg of CBD compared to placebo on wake after sleep onset (WASO) as assessed by actigraphy. | WASO is a parameter that examines the total amount of minutes awake after the first sleep epoch is achieved. Therefore, as the WASO increases, sleep efficiency decreases. | Baseline (week 0), week 8 | 
| To determine the effect of 8 weeks of 50mg or 100mg of CBD compared to placebo on Anxiety as assessed by the DASS-21 questionnaire. | Depression Anxiety Stress Scale-21 (DASS-21): A 21-item tool with subscales measuring the negative emotional states of depression, anxiety, and stress separately. Depression ranges from normal (0-9) to extremely severe (28+); anxiety ranges from normal (0-7) to extremely severe (20+); and stress ranges from normal (0-14) to extremely severe (34+). | Baseline (week 0), Week 4, week 8 | 
| To determine the effect of 8 weeks of 50mg or 100mg of CBD compared to placebo on Stress as assessed by the DASS-21 questionnaire. | Depression Anxiety Stress Scale-21 (DASS-21): A 21-item tool with subscales measuring the negative emotional states of depression, anxiety, and stress separately. Depression ranges from normal (0-9) to extremely severe (28+); anxiety ranges from normal (0-7) to extremely severe (20+); and stress ranges from normal (0-14) to extremely severe (34+). | Baseline (week 0), Week 4, week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CBD, Insomnia, sleep, fatigue, cannabidiol, mental health, anxiety