Stratification and Treatment in Early Psychosis Study - PROMOTE

What this study is about

The purpose of this trial is: * To investigate whether cannabidiol (CBD), compared to placebo, can reduce the severity of attenuated psychotic symptoms in individuals at clinical high risk for psychosis. * To confirm the safety of CBD in individuals at clinical high risk for psychosis. The trial is a randomised, double-blind, placebo-controlled, multi-centre, international clinical trial. Individuals meeting clinical high risk for psychosis criteria will be recruited for the trial intervention component of the trial. Participants are randomised to treatment with oral CBD 300mg (oral solution 100 mg/mL) twice daily, or a matching placebo, for 104 weeks. By using a battery of clinical outcome assessments, the trial will be able to assess several biomarkers to predict clinical outcomes and response to treatment with CBD. Participants will be invited to provide blood samples, stool samples, cerebrospinal fluid samples (if aged 18 years or over) and complete neuroimaging assessments. Individuals who are not found to have mental illness as defined by DSM-5 criteria will be recruited to a healthy control group, to validate the biomarker component of the trial. Additionally, a control group of healthy volunteers will be recruited who will not take the trial intervention to aid calibration between datasets from sites acquiring MRI data and to inform and validate any possible multivariate signature associated with the CHR-P state, course or outcome by understanding how these measures are different in controls. Healthy controls will also be used for secondary case-control comparisons. Healthy controls will undergo clinical and biomarker assessments only.

Who can join (things the study team will check)

✅ You may be able to join if…

• 12 to 35 years of age inclusive, willing and able to provide written informed consent/assent.
• Meet criteria for either the Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS) subgroups of the CHR-P state, defined using the CAARMS (PSYSCAN version), which also integrates the SIPS criteria. Inter-rater reliability will be ensured throughout via an ongoing training programme for the researchers at each site.
• The participant is currently not participating and is not expecting to start participation during the current trial in another intervention trial (e.g. medication, medical device, psychological intervention).
• Participants of childbearing potential* must be willing to ensure that they use highly effective contraception during the trial as per the requirements in the protocol**
• For participants who take part in the optional MRI scans: they must be eligible for MRI scanning as per local requirements, for example concerning implants or braces.
• For participants who take part in optional CSF collection: they must be aged 18 years or over, have excluded intracranial hypertension through MRI, be within the reference ranges in coagulation tests, have a BMI ≤32kg/m2, and have no medical or surgical conditions in which a lumbar puncture is contraindicated. The age range for eligibility has been applied as this corresponds to the usual age range for a clinical high-risk state; individual cases outside of this age range may have a different aetiology and/or prognosis which could impact on the trial outcomes. There is inadequate information on the effects of cannabidiol on the foetus in humans. Participants of childbearing potential* should use a highly effective method of contraception** for the duration of the trial and for 3 months after the last time the trial intervention was used. There is no special requirement for male participants to use highly effective contraception as there are no known safety concerns in males, such as sperm toxicity, as per the investigator's brochure. This trial will also not be collecting male participant partner pregnancy data. *A person is considered of childbearing potential, i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. ** Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: 1) combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral; intravaginal; transdermal); 2) progestogen-only hormonal contraception associated with inhibition of ovulation (oral; injectable; implantable); 3) intrauterine device (IUD); 4) intrauterine hormone-releasing system (IUS); 5) bilateral tubal occlusion; 6) vasectomised partner; 7) sexual abstinence (abstinence should only be used as a contraceptive method if it is in line with the participants' usual and preferred lifestyle). Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception. The participant agrees to use an acceptable method of contraception for the duration of the trial and for 3 months after any trial drug administration, unless surgically sterile or postmenopausal (no menses for 12 months without an alternative medical cause).

🚫 You may not be able to join if…

• Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures;*
• Pregnancy or breastfeeding;
• The participant is unable to fully comprehend the purpose of the trial or make a rational decision whether or not to participate;
• IQ<70 as measured by a validated IQ test e.g. WASI, WAIS, WISC, as approved for local languages and appropriate for the participant's age;
• Meeting DSM-5 criteria for substance use disorder, with the exception of nicotine use disorder (mild, moderate, and severe allowed). Mild cannabis use disorder is allowed (i.e. can meet up to but no more than 3 criteria on the SCID-5-RV) as long as the subject has not consumed cannabis on average more than three times a week in the past 30 days. Mild alcohol use disorder is also allowed;
• Antipsychotic exposure: any antipsychotic medication in the two weeks before screening at doses adequate for treating FEP (≥ minimum effective dose); or antipsychotic medication for longer than a cumulative total of 30 days in the 3 months before screening at doses adequate for treating FEP (≥ minimum effective dose);**
• Any past episode of frank psychosis (excluding BLIPS);
• Hypersensitivity to the active substance, sesame oil, sesame seed, or any of the excipients listed in section 3.3 of the IB;
• Current treatment with valproate (including valproic acid, sodium valproate, valproate semisodium);
• Current treatment with clobazam;
• Known hepatic insufficiency and/or transaminase levels exceeding the upper limit 2 times or more and bilirubin greater than 1.5 times the upper limit of normal;
• Active suicidal ideation within the past 2 weeks (a score of 1 or higher on CDSS question 8, followed by an assessment by the treating clinician who determines it is not safe for the patient to participate in the trial) or presence of risk (e.g. violence) ***;
• The participant has participated in another research study in which the participant received an experimental or investigational drug or intervention within 3 months before Visit 0;
• The participant refuses or cannot do any mandatory safety checks during the trial, specifically, refusal of: pregnancy test (those of childbearing potential only); safety blood tests; reporting of adverse events; or assessment of suicidality;
• Those of childbearing potential not willing to use a highly effective form of contraception during participation in the trial. There is inadequate information on the effects of cannabidiol on the foetus. Participants of childbearing potential should use a highly effective method of contraception for the duration of the main trial and for 3 months after any administration of trial intervention;
• Traumatic brain injury that is rated as 7 or above on the Traumatic Brain Injury screening instrument. Healthy controls:
  • Minor neurological disorders such as migraine, other minor headache disorders, sleep disorders or nerve palsies that are unlikely to affect trial or biomarker outcomes can be permitted.
  • If at screening, a potential participant is prescribed an antipsychotic at a dose ≥ minimum effective dose for treating FEP, they may be re-screened for trial participation at a later date if the dose is subsequently reduced below threshold for at least 2 weeks. Any decision to do so will be the responsibility of the treating clinician and must ensure that it is both safe and ethical to do so. Specialist advice will be made available and be provided by clinicians experienced in managing CHR-P at University of Oxford and King's College London.
  • The decision to include the patient is at the clinician's discretion. In case of a score of 1 or higher in CDSS question 8, the clinician can conclude that it is safe for the patient to participate after the patient is evaluated, in which case this exclusion criterion does not apply and the patient can participate. Either way, the treating clinician needs to record his/her evaluation of suicidal risk in the source documentation or medical file, including his/her considerations, and notify the site PI of the decision.

✅ You may be able to join if…

• 12 to 35 years old;
• Written informed consent/assent;
• Be assessed for the CHR-P state but do not meet CHR-P criteria: Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS) defined using the CAARMS;
• Be assessed with the SCID-5-RV and do not meet any diagnostic criteria of any Axis I psychiatric disorder.

🚫 You may not be able to join if…

• Lifetime history of a DSM Axis-I psychiatric disorder as determined by the SCID-5-RV;
• Lifetime history of meeting CHR-P state criteria;
• First-degree relative with a lifetime history of affective or non-affective psychosis (defined by treatment or diagnosis);
• Previous intake of antipsychotic medication at any dosage;
• Current intake of psychoactive medication;
• Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures;
• Pregnant or breastfeeding;
• Participant is unable to fully comprehend the purpose of the trial or make a rational decision whether or not to participate;
• IQ<70 as measured by a validated IQ test e.g. WASI, WAIS, WISC, as approved for local languages and appropriate for the participant's age;
• Any contraindications for MRI;
• Refusing to have their blood drawn and/or their MRI performed.

Where this trial is running

• MedUni Vienna, Department of Child and Adolescent Psychiatry, Vienna, Austria
• Douglas Hospital Research Centre, Montreal, Canada
• University Hospital Turku, Turku, Finland
• Vivantes Network for Health GmbH, Berlin, Germany
• University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany
• University Medical Center Schleswig-Holstein, Lübeck, Germany
• Ludwig Maximilian University Hospital, München, Germany
• National and Kapodistrian University of Athens, Athens, Greece
• University of Bari Aldo Moro, Bari, Italy
• University of Campania L. Vanvitelli, Naples, Italy
• University of Pavia, Pavia, Italy
• IRCCS Santa Lucia Foundation, Roma, Italy

+ 7 more sites.

Who to contact

Jared Robinson · +44 7900206137 · steptrials@phc.ox.ac.uk

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT07434973.