CANARY FAQs - clinicians

CANARY FAQs - clinicians

CANARY STUDY
FREQUENTLY ASKED QUESTIONS - CLINICIAN INFORMATION

What does ultra-high risk for psychosis mean?
A young person is considered to be at ultra-high risk (UHR) for psychosis if they experience a certain group of symptoms, and/or have particular family history traits, that are known to put people at a higher risk for developing a psychotic disorder than thegeneral population.

Symptoms vary for different individuals, but can include feeling low in mood, feeling paranoid or seeing things, or people hearing voices that they know aren’t there. Some people might worry that their thoughts are being heard, may not feel right in themselves, or might be having more difficulty than usual coping with work, school or relationships.

Other people within the UHR group may not experience any of these early symptoms, but have a family member with a psychotic disorder.

For some people, early symptoms will get worse without help. For others, the symptoms may lessen or simply go away. Because of these varied outcomes it is important to be able to provide a range of effective treatments to young people.

What treatments are there for symptoms experienced by young people who are at risk for psychosis?
There are two main categories of evidence-based treatments available – pharmacological treatments (medicines) and psychological therapies such as cognitive behavioural therapy (CBT).

Why is Orygen running this trial?
Current treatments don’t work for everyone so Orygen is investigating a potential new treatment known as cannabidiol. Orygen’s hope is that by testing potential new treatments we will be able to find effective treatments with limited side effects.

CANNABIDIOL

Is cannabidiol the same as cannabis or medical marijuana?
No. Cannabidiol is only one of many compounds found in the cannabis plant. Unlike other substances found in the cannabis plant (for example, tetrahydrocannabinol (THC), cannabidiol does not make people ‘high’.

Cannabidiol is extracted from the cannabis plant, purified and does not contain relevant quantities of other substances such as THC.

Aren’t there other drugs you can try? Why does it have to be cannabidiol?
Cannabidiol has been tested as a treatment for adult patients with psychotic disorders as well as in people with other illnesses such as epilepsy or anxiety. Because cannabidiol was found to reduce the severity of psychotic symptoms in adults with psychosis, it is important to test whether it is safe and effective in young people at UHR for psychosis.

Will the young people on the study get addicted to cannabidiol?
No. Unlike THC, cannabidiol is not addictive. In fact, it has been used to treat cannabis addiction in other research trials as it opposes some of the effects of THC.

How do you know for sure?
None of the previous studies have indicated that cannabidiol may be addictive in young people or adults.

What amount of cannabidiol will you be giving people?
Research participants will be randomly allocated to one of three groups:

-group one will take 1000mg daily of cannabidiol;

-group two will take 600mg daily of cannabidiol; and

-group three will take a placebo (no cannabidiol) each day for 12 weeks.

Orygen researchers decided on these doses based on previous studies testing cannabidiol in adult patients with psychosis, and studies testing cannabidiol in young people with anxiety and epilepsy.

How are you going to make sure participants don’t take more than that?
Trial participants will receive only a certain number of cannabidiol capsules at each study visit, or as appropriate to prescribe for that individual. In addition, Orygen researchers will monitor the number of capsules taken as well as blood levels of cannabidiol.

Will participants know which group they’re in?
No. Participants and researchers will not know which group each participant has been allocated to. Only the pharmacy will know this so they can provide the right medication. The reason for this is so that researchers can compare improvements of each group without jumping to conclusions based on how much CBD participants were taking.

How will you know if the cannabidiol is working?
Researchers and clinicians will use a range of psychiatric measures, including a questionnaire, to evaluate the effectiveness of cannabidiol. These are well- established approaches that are used in clinical research to measure improvements in symptoms.

Will people on the study be smoking the cannabidiol?
No. The cannabidiol will be administered as a capsule and cannot be smoked or inhaled. Capsules are self-administered by theparticipant.

Where is Orygen getting the cannabidiol from?
The cannabidiol used in our study is a natural product extracted from cannabis plants and is distributed by a European pharmaceutical company that specialises in cannabidiol.

Can someone continue using cannabidiol after the trial has concluded? If so, who will pay for it?
Cannabidiol can only be prescribed in Australia via a special access scheme and its cost is currently not subsidised by the Pharmaceutical Benefits Scheme. Trial participants who wish to access cannabidiol following the trial will need to cover the cost themselves. The research team encourages participants who are interested in continuing to take cannabidiol after the trial to speak to their general practitioner.

You can find more information about this here.

CLINICAL TRIAL

What’s a clinical trial?Clinical trials are systematic research investigations where new treatments or other interventions are tested in patients under the strict surveillance of one or more ethics committees. This trial will be run under the guidance of a human ethics committeeoperated by Melbourne Health.

How many people are going to be participating in the trial? 
The research team is planning to enrol up to 450 participants in this trial.

How long will the trial go for?
Participants will take the study medicine for 12 weeks, however follow-up assessments will continue over a period of up to two years. In total, Orygen researchers expect the trial to run for about four years.

Trial preparations began in July 2019, with recruitment of participants from June 2022.

The trial will finish around January 2026.

Where is the trial being run?
The trial is being conducted at the following centres:

In metropolitan Melbourne: Orygen Clinical Trials Unit in Parkville. 

In Western Australia and Queensland:

  • headspace Southport (Gold Coast, Queensland);
  • headspace Meadowbrook (Queensland);
  • headspace Redcliffe (Queensland);
  • headspace Strathpine (Queensland);
  • headspace Taringa (Queensland);
  • headspace Midland (Perth, Western Australia);
  • headspace Osborne Park (Perth, Western Australia);
  • headspace Joondalup (Perth, Western Australia); and 
  • Youth Axis (Perth, Western Australia).

CLINICIANS AND TRIAL PARTICIPATION

How do clinicians refer clients to this trial?
To participate in this trial, eligible participants based in Melbourne can self-refer or be referred by their clinician. A referral from the young person’s regular GP will be required prior to starting the study treatment. Outside of Melbourne only clients of the centres above can take part in the trial. However, the team encourages young people seeking support to contact their local headspace  centre. If you have a client you believe would be appropriate for this trial, you can contact us directly on canary@orygen.org.au

What age does someone have to be to take part in the trial?
Young people aged between 12 and 25, inclusive, can participate in the study.

Aren’t 12-year-olds too young to be having cannabidiol?
The age range of participants in this trial is similar to the age range of participants in other trials of cannabidiol (e.g., for epilepsy). It is important to know if this potential new treatment is effective for participants under the age of 18, as they represent a large proportion of headspace clients. Any participants aged under 18 will require the consent of their parent or guardian.

The client will be turning 26 soon, can they still be part of the trial?
Yes, if they are enrolled in the trial while still aged 25.

What happens if a participant begins the trial and decides  they don’t want to continue?
The study is voluntary, and all participants have the right to withdraw from the trial at any point. If a participant would like to withdraw, it is important for them to let the research assistant know to ensure the appropriate care can be provided.

What psychosocial support will a participant receive during the trial?
Participants will continue to receive treatment as usual with their current clinician. Participants in Melbourne who are not currently receiving psychosocial treatment will be engaged with a mental health clinician at Orygen’s Clinical Trials Unit for the duration of the study treatment period.

How will risk be managed for participants who are no longer engaged with a mental health service or provider whenfollow-up interviews are completed?
Participants will be assessed for risk at all follow-up research time-points. Participants identified as being at-risk or in distress will be provided crisis numbers and encouraged to engage with their general practitioner and the appropriate mental health service.

What do I need to do as a clinician of a participant?
There is no extra work for clinicians. All appointments, medication and biological samples are organised by the research assistants. The trial medication will be prescribed by the study doctor who will monitor safety and any unexpected adverse events. Research assistants or the study doctor will liaise with you if there is any concern regarding risk to the participant. If you have any concerns regarding the trial participant, please contact the study team on canary@orygen.org.au.

CANARY PARTICIPATION CRITERIA - INCLUSION AND EXCLUSION CRITERIA

INCLUSION CRITERIA
Eligible participants must:

  • be aged 12–25 years, inclusive;
  • be able to give informed consent (parent/guardian consent is required for those under 18 years);
  • be fluent in English;
  • meet one or more criteria for UHR groups (see below); and
  • have attenuated psychotic symptoms at UHR level present in the past month (see below).

OPERATIONALISED UHR INTAKE CRITERIA

Group 1: Vulnerability Group

Family history of psychosis in first degree relative OR Schizotypal Personality Disorder (as defined by DSM V) in identified patient AND Drop in Functioning:

Recency: Change in functioning occurred within past year

Impact: SOFAS score at least 30% below previous level of functioning and sustained for at least one month. OR Sustained low functioning:

Recency: For the past 12 months or longer
Impact: SOFAS score of 50 or less.

Group 2: Attenuated Psychotic Symptoms Group 

2a)Subthreshold intensity:

Intensity: Global Rating Scale Score of 3-5 on Unusual Thought Content subscale, 3-5 on Non-Bizarre Ideas subscale, 3-4 on Perceptual Abnormalities subscale and/or 4-5 on Disorganised Speech subscales of the CAARMS

Frequency: Frequency Scale Score of 3-6 on Unusual Thought Content, Non-Bizarre Ideas, Perceptual Abnormalities and/or Disorganised Speech subscales of the CAARMS

Duration: symptoms present for at least one week Recency:symptoms presentin past year

2b) Subthreshold frequency:

Intensity: Global Rating Scale Score of 6 on Unusual Thought Content subscale, 6 on Non-Bizarre Ideas subscale, 5-6 on Perceptual Abnormalities subscale and/or 6 on Disorganised Speech subscales of the CAARMS

Frequency: Frequency Scale Score of 3 on Unusual Thought Content, Non-Bizarre Ideas, Perceptual Abnormalities and/or Disorganised Speech subscales of the CAARMS

Recency: symptoms present in past year

Group 3: BLIPS Group

Intensity: Global Rating Scale Score of 6 on Unusual Thought Content subscale, 6 on Non-Bizarre Ideas subscale, 5 or 6 on Perceptual Abnormalities subscale and/or 6 on Disorganised Speech subscales of the CAARMS

Frequency: Frequency Scale Score of 4-6 on Unusual Thought Content, Non-Bizarre Ideas, Perceptual Abnormalities and/or Disorganised Speech subscales Duration: Symptoms present for less than one week and spontaneously remit on every occasion.

Recency: symptoms present in past year

EXCLUSION CRITERIA

Participants are unable to participate in the study if:

  • their psychotic symptoms are only present during acute intoxication;
  • they’ve been prescribed psychotropic medication, including antidepressants, and a stable dose has not been maintained for more than six weeks prior to randomisation (baseline assessment, not the start of the lead-in phase). Antipsychotic medication is not permitted during the trial and must be ceased prior to the lead-in assessment).
  • they’re pregnant, lactating or (if sexually active) not on effective contraception;
  • clinical blood test findings might compromise participant safety or confound trial results;
  • they are experiencing an acute or unstable systemic medical disorder;
  • ​they have a psychiatric condition due to a medical condition;
  • experience severe disturbance resulting in inability to comply with informed consent or the treatment protocol;
  • they have a current or historical diagnosis of serious developmental disorder; or
  • they have previously experienced a psychotic episode lasting one week or longer.

DISCONTINUATION AND WITHDRAWAL

Voluntary discontinuation
Participants are free to withdraw their participation in the study at any time.

Participants who discontinue will be asked about the reason(s) for discontinuation and about the presence of any medical concerns. Any remaining medication will be returned and recorded.

Any medical concerns will be followed up until resolution, stabilisation or the participant is unable to be contacted.

Discontinuation criteria
A participant will be considered ‘discontinued’ from the study when they have stopped study medication. However, the participant may continue to complete other aspects as per the study schedule.

A participant will be discontinued when:

  • participation interferes with the appropriate clinical management of risk to self or others;
  • an adverse event leads to a request for discontinuation by the participant or investigator;
  • a participant becomes pregnant;
  • a participant is not compliant with the medication;
  • a participant starts non-trial psychotropic medication or changes dose of existing psychotropic medication;
  • the randomisation code is broken;
  • the investigator judges there has been severe non-compliance to the study protocol; or
  • the participant transitions to psychosis or mania. Transition is operationally defined via the Comprehensive Assessment of At-Risk Mental States  (CAARMS) tool, as frank positive psychotic symptoms occurring daily for one week or longer.

Withdrawal criteria
A participant will be considered ‘withdrawn’ from the study in cases where all involvement is ceased.

Withdrawal from the trial will occur if consent is withdrawn either by the participant or their parent/guardian. Participants who withdraw from the study will be asked about the reason(s) for their withdrawal and about the presence of any medical concerns.

Medication will be ceased at the time of withdrawal from the study. Any remaining medication will be returned and recorded by the research assistant and pharmacy.

Participation in safety assessments with the study doctor will be offered to participants who withdraw from the study.

SEP v3.0 140622. HREC/60933/MH-2020