Stratification and Treatment in Early Psychosis Study - PROMOTE

NCT07434973 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: PID-187251006894
• Study Type: interventional
• Target: 586
• Locations: 10 countries
• Sites: 19

Brief Summary

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.

Conditions

Clinical High Risk for Psychosis (CHR); Clinical High Risk for Psychosis; Clinical High Risk for Developing Psychosis

Keywords

STEP-PROMOTE; PROMOTE; CHR-P; Clinical High Risk for Psychosis; psychosis

Outcome Measures

Primary Outcomes (1)

• ChaChange from baseline in attenuated positive psychotic symptoms (CAARMS P1-P4 positive symptom subscale score)

  Change from baseline to Week 104 in the positive symptom subscale score (P1-P4) of the Comprehensive Assessment of At-Risk Mental States (CAARMS). Higher scores indicate greater symptom severity.

  Baseline to Week 104

Secondary Outcomes (43)

• Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)

  Baseline to Week 4

• Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)

  Baseline to Week 4

• Change in distress associated with attenuated psychotic symptoms

  Baseline to Week 4

• Change in anxiety symptoms (Hamilton Anxiety Rating Scale, HAM-A)

  Baseline to Week 4

• Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)

  Baseline to Week 4

Study Arms (3)

Cannabidiol 100g/ml oral solution

ACTIVE COMPARATOR

Participants will take the intervention for 106 weeks (104 weeks plus a 2-week taper). Doses depend on age and weight: Adults (16 years and older) over 50kg: daily dose 600mg (6ml); 300mg (3ml) twice a day (b.i.d); Adults (16 years and older) less than 50kg: daily dose 10mg/kg; 5mg/kg twice a day (b.i.d); Children (\<16 years old): daily dose 5mg/kg twice a day (b.i.d), following on from a two-week rapid titration schedule. n=188

Drug: Cannabidiol (CBD)

Placebo

PLACEBO COMPARATOR

Participants will take the intervention for 106 weeks (104 weeks plus a 2-week taper). Doses depend on age and weight: Adults (16 years and older) over 50kg: daily dose 600mg (6ml); 300mg (3ml) twice a day (b.i.d). Adults (16 years and older) less than 50kg: daily dose 10mg/kg; 5mg/kg twice a day (b.i.d). Children (\<16 years old): daily dose 5mg/kg twice a day (b.i.d), following on from a two-week rapid titration schedule. n=188

Drug: Placebo

Healthy controls

NO INTERVENTION

A healthy control in the context of this trial is someone who does not meet CHR-P criteria or have a diagnosis of a mental health condition. They will not take the trial intervention and attend one trial visit for clinical assessments and biomarker sampling only. n=150

Interventions

Cannabidiol (CBD) DRUG

CBD 100 mg/mL Oral Solution

Cannabidiol 100g/ml oral solution

Placebo DRUG

Placebo for Cannabidiol oral solution 100mg/mL oral solution

Placebo

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 qualify 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;

Sponsors & Collaborators

• University of Oxford: lead
• Wellcome Trust: collaborator
• Jazz Pharmaceuticals: collaborator

Study Sites (19)

MedUni Vienna, Department of Child and Adolescent Psychiatry

Vienna, Austria

Location

Douglas Hospital Research Centre

Montreal, Canada

Location

University Hospital Turku

Turku, Finland

Location

Vivantes Network for Health GmbH

Berlin, Germany

Location

University of Cologne, Faculty of Medicine and University Hospital of Cologne

Cologne, Germany

Location

University Medical Center Schleswig-Holstein

Lübeck, Germany

Location

Ludwig Maximilian University Hospital

München, Germany

Location

National and Kapodistrian University of Athens

Athens, Greece

Location

University of Bari Aldo Moro

Bari, Italy

Location

University of Campania L. Vanvitelli

Naples, Italy

Location

University of Pavia

Pavia, Italy

Location

IRCCS Santa Lucia Foundation

Roma, Italy

Location

Stichting Amsterdam UMC

Amsterdam, Netherlands

Location

Biobizkaia Health Research Institute (Asociación Instituto de Investigación Sanitaria)

Bilbao, Spain

Location

Foundation for Biomedical Research of the Gregorio Marañón Hospital (FIBHGM)

Madrid, Spain

Location

Psychiatric University Hospital (PUK)

Zurich, Switzerland

Location

Cambridgeshire and Peterborough NHS Foundation Trust

Cambridge, United Kingdom

Location

Institute of Psychiatry, Psychology & Neuroscience, King's College London

London, United Kingdom

Location

Oxford Health NHS Foundation Trust (OHFT)

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Psychotic Disorders

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Philip McGuire, PhD, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jared Robinson

CONTACT

+44 7900206137; steptrials@phc.ox.ac.uk

Jennifer Davies

CONTACT

steptrials@phc.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: February 27, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: February 27, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data and supporting documents will become available once the primary papers are available in the scientific domain.
• Access Criteria: These will be provided by the sponsor to the requesting party.

Locations

ES (2); AU (1); GR (1); CA (1); DE (4); NL (1); CH (1); FI (1); GB (3); IT (4)