Cannabidiol for At Risk for psychosis Youth

CanARY is a Randomised Controlled Trial examining the feasibility of Cannabidiol (CBD) as a treatment for young people aged 12 - 25 years who have been identified as Ultra-High Risk of Psychosis. CanARY is a three-arm RCT with a placebo and 2 discrete drug doses randomised to the ratio 1:1:1. The study is double-blind. Participants will be asked to take the study intervention for 12 weeks. CBD (per oral) – doses of 600mg or 1000mg per day (fixed schedule) for 12 weeks - All participants will take 2x capsules in the morning and 3x capsules in the evening. - For the 1000mg group each capsule will contain 200mg active CBD - For the 600mg group 1x morning capsule will contain 200mg active CBD and 1x will be placebo; 2x evening capsules will each contain 200mg active CBD and 1x will be placebo - For the placebo group all capsules will be placebo Both placebo and the active are formulated in hard gelatin capsules, each placebo capsule contains 600mg Softisan 378. Within the first week, the study doctor will call the participant to monitor compliance and check for any side effects. Adherence to the study medication will be assessed by pill counts upon return of medication to the Research Assistant. Pill count verification will also be conducted by the pharmacy and a subset of these data by the unblinded monitor. Additionally, medication diaries (mobile applications) and e-reminder systems will be used to facilitate and document treatment adherence. Objective quantification of cannabinoid levels will be obtained via regular urine samples throughout the treatment phase. Where a participant fails to present to the treatment clinic (site) for visits where an intervention is administered, details of this protocol deviation will be recorded in the source documentation with the reason for the failure to present to the clinic explained where possible. Clinical case management and psychological intervention will be continued as 'Treatment as Usual' in addition to pharmacological intervention. All participants will complete interviews at set time points: baseline, week 4, week 8 and week 12. Participants will also be provided the opportunity to complete a follow-up interview at week 26. Lead-in Young people aged 12-25 years who are interested in taking part in the study will be offered an initial appointment with a researcher. At this visit, the young person will be provided with information about the study, including the interventions, research assessments, time commitment, risks and benefits. At the lead-in visit, a researcher will explain the study and provide the participant (and their parent(s)/legal guardian for participants under the age of 18) with a copy of the consent form. If the participant (and their parent(s)/legal guardian for participants under the age of 18) give consent to take part in the trial, the researcher will then complete a demographic questionnaire, the Social and Occupational Functioning Assessment Scale (SOFAS), the Comprehensive Assessment of At-Risk Mental States (CAARMS), and the Structured Clinical Interview for DSM-5 – Schizotypal Personality Disorder Module (SCID-II) with the participant. The researcher will explain that participation in the trial is contingent on inclusion and exclusion criteria to be reviewed at the subsequent Screening visit and the persistence of UHR criteria until the Screening visit. The lead-in visit takes approximately 2 hours. Screening Visit: The Screening visit includes a review of the inclusion and exclusion criteria, medical history, physical examination, blood (fasted for 4-10 hours prior) and urine tests, and the CAARMS. A researcher will inform the participant about their eligibility to take part in the trial at the end of the Screening visit or as soon as the study doctor has confirmed the eligibility of the participant. The Screening visit will take approximately 2-3 hours. Baseline (Week 0) At the Baseline assessment, the inclusion and exclusion criteria and concomitant medication will be reviewed before the first 4 weeks of the investigational product (IP) is dispensed along with detailed instructions on how to take the IP. Rating scales (CAARMS, Montgomery Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Overall Anxiety Severity And Impairment Scale (OASIS), the Brief Psychiatric Rating Scale (BPRS), Negative Symptoms Inventory-Psychosis Risk (NSI-PR), Treatment Expecation Questionnaire (TEX-Q), the Patient Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD, SOFAS, Clinical Global Impressions Scale (CGI), Assessment of Quality of Life-8D (AQoL-8D), Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Resource Use Questionnaire (RUQ), COVID-19 questionnaire and Structured Clinical Interview for DSM-5 (SCID-I)) will be completed as part of the Baseline visit and a hair sample will be collected. The Baseline assessment also includes a review of adverse events. The Baseline visit takes approximately 2 – 3 hours. Week 4 The Week 4 visit includes a review of adverse events and a physical examination, the CAARMS, MADRS, HAM-A, OASIS, BPRS, PROMIS-SD, NSI-PR, SOFAS, CGI, AQoL-8D and ASSIST. The IP will be dispensed and any remaining IP from the Baseline visit returned and medication adherence will be recorded. Blood (fasted for 4-10 hours prior) and urine samples will be collected at this study visit. The Week 4 visit takes approximately 1.5 – 2 hours. Week 8 The Week 8 visit includes a review of adverse events and completion of the CAARMS, MADRS, HAM-A, OASIS, SOFAS, CGI, AQoL-8D, PROMIS-SD, BPRS, NSI-PR and ASSIST. The IP will be dispensed and any remaining IP from the previous visit returned. Medication adherence will be recorded at the Week 8 visit and a urine sample collected. The Week 8 visit takes approximately 1.5 hours. Week 12 The Week 12 visit includes a review of adverse events and a physical examination, the CAARMS, MADRS, HAM-A, OASIS, SOFAS, CGI, ASSIST, PROMIS-SD, BPRS, NSI-PR, AQoL-8D, RUQ and SCID-I. Any remaining IP from the Baseline visit returned and medication adherence will be monitored. Blood (fasted for 4-10 hours prior), urine and hair samples will be collected. If the participant is in the PK study, the week 12 main study bloods will be collected at the research clinic at the ‘2 hours prior to final dose’ time point (the first bloods collected on that day). The Week 12 visit takes approximately 2 hours. Week 26 - Week 104 Give the study duration of 3.5 years, including a recruitment period of 3 years, not all participants will have week 56, week 78 or week 104 data collected. The length of time the young person is followed up for will depend on when the participant is recruited in the study. All participants will be followed-up to complete the week 26 visit. Participants will be asked if they are agreeable to be followed up for the 6 month, 12 month, 18 month and 24 month assessments to provide comprehensive results on the effectiveness and longevity of CBD. Participants can nominate not to complete these assessments. The follow-up visits (Week 26, 52, 78 and 104) will include a review of adverse events and concomitant medication, and the administration of the CAARMS, MADRS, HAM-A, OASIS, SOFAS, CGI, ASSIST, AQoL-8D, PROMIS-SD, BPRS, RUQ, NSI-PR and SCID-I mood and psychosis modules* (*Week 26 only). These visits will take approximately 1 (Week 26 and 78) and 2 (Week 52 and 104) hours.