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Trial registered on ANZCTR


Registration number
ACTRN12624000236594
Ethics application status
Approved
Date submitted
21/09/2023
Date registered
11/03/2024
Date last updated
11/03/2024
Date data sharing statement initially provided
11/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Treating anxiety in young people (12-25 years) using Cannabidiol (CBD) when conventional anxiety treatments have proven ineffective.
Scientific title
Efficacy of Cannabidiol for Youth with Inadequate Clinical Response to Anxiety Treatments - A Randomised Controlled Trial
Secondary ID [1] 310607 0
26538
Universal Trial Number (UTN)
U1111-1297-9302
Trial acronym
CANCAN
Linked study record
ACTRN12617000825358 is the pilot study of this current RCT

Health condition
Health condition(s) or problem(s) studied:
Anxiety 331485 0
Treatment-Resistant Anxiety 331486 0
Condition category
Condition code
Mental Health 328214 328214 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The CANCAN Study is a double-blind, randomised, placebo-controlled two-armed trial investigating the benefits of 600-800mg/day Cannabidiol (CBD) in 180 young people with a current diagnosis of an anxiety disorder without clinically meaningful improvement in response to standard care.

Intervention: CBD or placebo (per oral) – doses of 600-800 mg per day (fixed-flexible schedule) for 12 weeks. Capsules contain 200mg active CBD or placebo. Doses will start at 600 mg per day (1 capsule in the morning, 2 capsules at night). Participants are seen by the study doctor every 4 weeks throughout the study. At week 4 or 8, in participants who are considered not “much improved” by the study doctor (i.e., CGI-I score >2) the daily dose will be increased from 3 to 4 capsules if tolerated (2 capsules twice a day). All study participants will also receive psychosocial treatment (here referred to as treatment as usual, TAU) for the duration of the trial. TAU may vary across participants as clinically indicated depending on individual need. The specific type of psychosocial treatment and number of treatment sessions will be documented at every study visit.

Adherence to the study medication will be assessed by pill counts upon return of medication to the Research Assistant or pharmacist. Pill count verification will also be conducted by the pharmacy and a subset of this data by the unblinded monitor. Objective quantification of cannabinoid levels will be obtained via regular urine samples throughout the treatment phase.
Intervention code [1] 327012 0
Treatment: Drugs
Comparator / control treatment
Placebo and treatment as usual (TAU). Participants in the control arm of the trial will receive a matching placebo for all capsules. The placebo treatment consists of a hard wax capsule

State of the art TAU for anxiety disorders includes psychosocial therapy (such as CBT) delivered by a mental health professional and/or antidepressant treatment. All interventions delivered will be documented.
Control group
Placebo

Outcomes
Primary outcome [1] 336087 0
Change in the Overall Anxiety Severity and Impairment Scale (OASIS) score between baseline and 12 weeks.
Timepoint [1] 336087 0
Screening, Baseline, Week 4, Week 8, Week 12 post-baseline
Secondary outcome [1] 426808 0
The QIDS-A17-C assesses the criterion symptom domains for DSM-5 major depressive disorder.
Timepoint [1] 426808 0
Screening, Baseline, Week 4, Week 8, Week 12 post-baseline
Secondary outcome [2] 426809 0
The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was developed for the World Health Organization (WHO) by an international group of substance abuse researchers to detect and manage substance use and related problems in primary and general medical care settings.
Timepoint [2] 426809 0
Screening, Baseline, Week 4, Week 8, Week 12 post-baseline
Secondary outcome [3] 426810 0
The Clinical Global Impressions (CGI) Scale is a standardised assessment tool. Its goal is to allow the clinician to rate the severity of illness, change over time, and efficacy of medication, considering the patient’s clinical condition and the severity of side effects. This will be assessed as a composite outcome.
Timepoint [3] 426810 0
Screening, Baseline, Week 4, Week 8, Week 12 post-baseline
Secondary outcome [4] 426811 0
The Social and Occupational Functioning Assessment Scale (SOFAS) is a numeric scale (1 through 100) used to rate subjectively the social, occupational, and psychological functioning. This will be assessed as a composite outcome
Timepoint [4] 426811 0
Baseline, Week 4, Week 8, Week 12 post-baseline
Secondary outcome [5] 426812 0
The Assessment of Quality of Life-6D (AQoL-6D) instrument measures health-related Quality of Life. The AQoL-6D is a self-report questionnaire adapted for adolescents that assesses the quality of life relative to six dimensions: Independent living, Relationships, Senses Mental health, Pain and Coping.
Timepoint [5] 426812 0
Baseline, Week 4, Week 8, Week 12 post-baseline
Secondary outcome [6] 426813 0
Resource Use Questionnaire (RUQ) estimates the costs of seeking help including health care, welfare, and employment productivity. This will be assessed as a composite outcome.

Timepoint [6] 426813 0
Baseline, Week 12 post-baseline
Secondary outcome [7] 429655 0
Anxiety symptoms will be assessed by the Hamilton Anxiety Rating Scale (HAM-A). It is clinician-rated and consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety and somatic anxiety. This will be assessed as a composite outcome.
Timepoint [7] 429655 0
Baseline, Week 4, Week 8, Week 12 post-baseline

Eligibility
Key inclusion criteria
1. Aged 12-25 (inclusive) at entry;
2. Ability to give informed consent and adhere to study procedures (parental or guardian consent will be obtained for those aged <18 years);
3. Sufficient fluency in English (for assessment purposes);
4. Diagnosis of a DSM-5 anxiety disorder (i.e., social anxiety disorder, panic disorder, separation anxiety disorder, specific phobia, agoraphobia, generalized anxiety disorder);
5. Anxiety symptoms and functional impairment despite receiving TAU for at least 2 months, indicated by a score of greater than or equal to 10 on the OASIS, and lack of clinically meaningful improvement (CGI-I score = 2).
Minimum age
12 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior sensitivity or allergy to cannabidiol (CBD) or any cannabis-derived product;
2. Current treatment with anxiolytic medication e.g. benzodiazepines or beta blockers;
3. If prescribed permitted psychotropic (e.g. antidepressant medication), the individual has not been on a stable dose for a minimum of 4 weeks;
4. Pregnancy, lactation, or if sexually active, no effective contraception;
5. Clinical blood test findings that might compromise participant safety or confound the trial results;
6. History of DSM-5 schizophrenia spectrum, delusional, bipolar I disorder, or current substance/medication induced psychotic disorder;
7. Acute or unstable systemic medical disorder;
8. Any metabolic, endocrine or other physical illness, e.g. thyroid disease, with neuropsychiatric consequences which may compromise the safety of the participant or the conduct of the trial;
9. Acute suicidality (indicated by a score of 3 on QIDS-A17-C item 13) or severe depression (indicated by a score of >20 on the QIDS-A17-C );
10. Severe disturbance, such that the person is unable to comply with either the requirements of informed consent or the treatment protocol.

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)
The allocation sequence will be concealed within a web-based Research Project Management System that has been purpose built by the Sponsor Orygen.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be based on a permutated block randomisation scheme with stratification for site and severity of depression (Scores on the QIDS-A17-C ranging from 0 to 10 will be categorised as ‘no’ or 'mild' depression, while scores equal to or greater than 11 will be classified as 'moderate' or ‘severe’ depression). The randomisation sequence will be computer-generated by a statistician who is independent of the day-to-day conduct of the trial.
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 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The main analysis will be based on all randomised participants with at least one post-baseline observation (intention-to-treat population). The primary efficacy analysis will assess average treatment group differences for the primary outcome measure (OASIS total score) over the entire study period and will use a likelihood based mixed-effects model, repeated measures approach (MMRM). The MMRM model includes the fixed, categorical effects of treatment, visit, and treatment-by-visit interaction. Site will also be included. Planned comparisons will be carried out with the MMRM models to determine between group differences in change of anxiety symptoms from baseline to week 12. Differences between treatment groups in terms of secondary outcome measures (HAM-A, QIDS-A17-C, ASSIST, SOFAS scores) will be examined using MMRM as per the primary outcome. Categorical variables will be summarised using frequency and percentage. Improvement in CGI-I and diagnostic remission at 12 weeks, measured as binary variables, will be compared between the treatment and comparator arms through calculation of the relative risk and risk difference.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC

Funding & Sponsors
Funding source category [1] 314821 0
Government body
Name [1] 314821 0
The Medical Research Future Fund (MRFF) Department of Health and Aged Care
Country [1] 314821 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Orygen Centre for Youth Mental Health
Address
35 Poplar Road, Parkville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 316811 0
None
Name [1] 316811 0
Address [1] 316811 0
Country [1] 316811 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313826 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 313826 0
The University of Melbourne Grattan Street, Parkville Victoria, 3010, Australia
Ethics committee country [1] 313826 0
Australia
Date submitted for ethics approval [1] 313826 0
28/08/2023
Approval date [1] 313826 0
24/10/2023
Ethics approval number [1] 313826 0

Summary
Brief summary
Anxiety disorders are one of the most common mental health conditions in young people, affecting around 7% of adolescents in Australia. Yet, the rate of inadequate treatment response and corresponding functional impairment in anxiety is high. Cannabidiol (CBD), a main component of Cannabis, can effectively reduce anxiety in adults with social anxiety disorder and has found to be safe and well tolerated in children and adolescents with epilepsy. The current study team have previously tested CBD (up to 800 mg/day for 12 weeks) in a pilot study involving in 31 individuals (mean 21 yrs) with treatment resistant anxiety disorders (ACTRN12617000825358). Two-thirds of participants had a >33% reduction in anxiety severity and 40% of participants had >50% reduction at 12 weeks. CBD was well tolerated with no severe, or unexpected adverse events; 94% of participants completed the intervention, indicating high acceptability. Thus, CBD may be a suitable candidate intervention for youth with inadequate response to anxiety treatments. This is a two-armed randomised control trial in 180 young people with a treatment-resistant anxiety disorder aged 12-25 years, randomised to receive CBD (600mg -800mg/d) or placebo equivalent at a 1:1 ratio, for 12 weeks. Ethics approval was received on 24/10/2023.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38594 0
Prof Paul Amminger
Address 38594 0
Orygen 35 Poplar Road, Parkville, VICTORIA 3052
Country 38594 0
Australia
Phone 38594 0
+61 03 9966 9421
Fax 38594 0
Email 38594 0
[email protected]
Contact person for public queries
Name 38595 0
Shelley Baird
Address 38595 0
Orygen 35 Poplar Road, Parkville, VICTORIA 3052
Country 38595 0
Australia
Phone 38595 0
+61 0401772657
Fax 38595 0
Email 38595 0
[email protected]
Contact person for scientific queries
Name 38596 0
Paul Amminger
Address 38596 0
Orygen 35 Poplar Road, Parkville, VICTORIA 3052
Country 38596 0
Australia
Phone 38596 0
+61 03 9966 9421
Fax 38596 0
Email 38596 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
Consent will not be sought for IPD sharing


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.