Stratification and Treatment in Early Psychosis Study - PROMOTE (STEP-PROMOTE)

February 19, 2026 updated by: University of Oxford

ImPRoving OutcoMes in Individuals at Clinical High Risk fOr Psychosis Using Cannabidiol: a Double-blind, Randomised conTrollEd Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

586

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Vienna, Austria
  • Canada
  • Finland
      • Turku, Finland
        • University Hospital Turku
        • Contact:
        • Principal Investigator:
          • Jarmo Hietala
  • Germany
  • Greece
      • Athens, Greece
        • National and Kapodistrian University of Athens
        • Principal Investigator:
          • Nikos Stefanis
        • Contact:
  • Italy
      • Bari, Italy
      • Napoli, Italy
        • University of Campania L. Vanvitelli
        • Contact:
        • Principal Investigator:
          • Armida Mucci
      • Pavia, Italy
      • Roma, Italy
  • Netherlands
      • Amsterdam, Netherlands
  • Spain
      • Bilbao, Spain
        • Biobizkaia Health Research Institute (Asociación Instituto de Investigación Sanitaria)
        • Contact:
        • Principal Investigator:
          • Ana Catalan
      • Madrid, Spain
        • Foundation for Biomedical Research of the Gregorio Marañón Hospital (FIBHGM)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Celso Arango
  • Switzerland
      • Zurich, Switzerland
        • Psychiatric University Hospital (PUK)
        • Contact:
        • Principal Investigator:
          • Philipp Homan
  • United Kingdom
      • Cambridge, United Kingdom
        • Cambridgeshire and Peterborough NHS Foundation Trust
        • Contact:
      • London, United Kingdom
        • Institute of Psychiatry, Psychology & Neuroscience, King's College London
        • Principal Investigator:
          • Paolo Fusar-Poli
        • Contact:
      • Oxford, United Kingdom

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Description

CHR-P patients:

Inclusion Criteria

  1. 12 to 35 years of age inclusive, willing and able to provide written informed consent/assent.
  2. 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.
  3. 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).
  4. 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**
  5. 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.
  6. 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).

Exclusion Criteria

  1. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures;*
  2. Pregnancy or breastfeeding;
  3. The participant is unable to fully comprehend the purpose of the trial or make a rational decision whether or not to participate;
  4. 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;
  5. 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;
  6. 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);**
  7. Any past episode of frank psychosis (excluding BLIPS);
  8. Hypersensitivity to the active substance, sesame oil, sesame seed, or any of the excipients listed in section 3.3 of the IB;
  9. Current treatment with valproate (including valproic acid, sodium valproate, valproate semisodium);
  10. Current treatment with clobazam;
  11. 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;
  12. 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) ***;
  13. 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;
  14. 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;
  15. 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;

  16. Traumatic brain injury that is rated as 7 or above on the Traumatic Brain Injury screening instrument.

    • 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.

Healthy controls:

Inclusion Criteria

  1. 12 to 35 years old;
  2. Written informed consent/assent;
  3. 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;
  4. Be assessed with the SCID-5-RV and do not meet any diagnostic criteria of any Axis I psychiatric disorder.

Exclusion Criteria

  1. Lifetime history of a DSM Axis-I psychiatric disorder as determined by the SCID-5-RV;
  2. Lifetime history of meeting CHR-P state criteria;
  3. First-degree relative with a lifetime history of affective or non-affective psychosis (defined by treatment or diagnosis);
  4. Previous intake of antipsychotic medication at any dosage;
  5. Current intake of psychoactive medication;
  6. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures;
  7. Pregnant or breastfeeding;
  8. Participant is unable to fully comprehend the purpose of the trial or make a rational decision whether or not to participate;
  9. 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;
  10. Any contraindications for MRI;
  11. Refusing to have their blood drawn and/or their MRI performed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cannabidiol 100g/ml oral solution

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)
CBD 100 mg/mL Oral Solution
Placebo Comparator: Placebo

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
Placebo for Cannabidiol oral solution 100mg/mL oral solution
No Intervention: Healthy controls

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ChaChange from baseline in attenuated positive psychotic symptoms (CAARMS P1-P4 positive symptom subscale score)
Time Frame: Baseline to Week 104
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in CAARMS (Comprehensive Assessment of At-Risk Mental States) total score
Baseline to Week 4
Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Comprehensive Assessment of At-Risk Mental States (CAARMS) P1-P4 subscale scores.
Baseline to Week 4
Change in distress associated with attenuated psychotic symptoms
Time Frame: Baseline to Week 4
Change from in Comprehensive Assessment of At-Risk Mental States (CAARMS) distress scores.
Baseline to Week 4
Change in anxiety symptoms (Hamilton Anxiety Rating Scale, HAM-A)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Hamilton Anxiety Rating Scale (HAM-A) total score.
Baseline to Week 4
Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Overall Anxiety Severity and Impairment Scale (OASIS) score
Baseline to Week 4
Remission from Clinical High-Risk for Psychosis (CHR-P) state
Time Frame: Baseline to Week 4
Proportion of participants meeting Comprehensive Assessment of At-Risk Mental States (CAARMS) remission criteria at Week 4.
Baseline to Week 4
Change in quality of life (EQ-5D-3L index score)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in EQ-5D-3L index score.
Baseline to Week 4
Change in quality of life (WHOQOL-BREF total score)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in WHOQOL-BREF total score.
Baseline to Week 4
All-cause treatment discontinuation
Time Frame: Baseline to Week 4
Proportion of participants who discontinue study treatment for any reason by Week 4.
Baseline to Week 4
Incidence of adverse events
Time Frame: Baseline to Week 4
Number of participants with one or more adverse events by Week 4.
Baseline to Week 4
Severity of adverse events (Glasgow Antipsychotic Side-effect Scale, GASS total score)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Glasgow Antipsychotic Side-effect Scale (GASS) total score.
Baseline to Week 4
Change in clinician-rated global severity (Clinical Global Impressions (CGI) scale- - Severity, CGI-S)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Clinical Global Impressions scale- - Severity (CGI-S) score.
Baseline to Week 4
Change in clinician-rated global severity (Clinical Global Impressions (CGI) scale- - Improvement, CGI-I)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Clinical Global Impressions scale- - Improvement (CGI-I) score.
Baseline to Week 4
Change in patient-rated global severity (Patient Global Imression of Improvement, PGI-I)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Patient Global Imression of Improvement (PGI-I) score.
Baseline to Week 4
Change in patient-rated global severity (Patient Global Impression of Severity, PGI-S)
Time Frame: Baseline to Week 4
Change from baseline to Week 4 in Patient Global Imression of Severity (PGI-S) score.
Baseline to Week 4
Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in anxiety symptoms (Hamilton Anxiety Rating Scale , HAM-A)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in global functioning (Social and Occupational Functioning Assessment Scal, SOFAS)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in cognitive functioning (PsyCog battery composite score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Transition to psychosis
Time Frame: Baseline to Week 104
Proportion of participants meeting Comprehensive Assessment of At-Risk Mental States (CAARMS) criteria for transition to psychosis. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.
Baseline to Week 104
Remission from Clinical High-Risk for Psychosis (CHR-P) state
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in quality of life (EQ-5D-3L)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in quality of life (WHOQOL-BREF)
Time Frame: Baseline to Week 104
Baseline to Week 104
All-cause treatment discontinuation
Time Frame: Baseline to Week 104
Baseline to Week 104
Incidence of adverse events
Time Frame: Baseline to Week 104
Baseline to Week 104
Severity of adverse events (Glasgow Antipsychotic Side-effect Scale, GASS)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in clinician-rated global impression (CGI)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in patient-rated global impression (PGI)
Time Frame: Baseline to Week 104
Baseline to Week 104
Diagnosis of mental disorders
Time Frame: Baseline, Week 104, and 4 years post-baseline
Proportion of participants diagnosed with a mental disorder based on clinical record review. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.
Baseline, Week 104, and 4 years post-baseline
Prescription of psychotropic medication
Time Frame: Baseline, Week 104, and 4 years post-baseline
Proportion of participants prescribed psychotropic medication. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.
Baseline, Week 104, and 4 years post-baseline
Psychiatric hospital or emergency department admission
Time Frame: Baseline, Week 104, and 4 years post-baseline
Proportion of participants admitted to psychiatric hospital or emergency services. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.
Baseline, Week 104, and 4 years post-baseline
Number of healthcare appointments
Time Frame: Baseline to 4 years post-baseline
Total number of healthcare appointments recorded. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.
Baseline to 4 years post-baseline
Mortality (including suicide)
Time Frame: Baseline to 4 years post-baseline
All-cause mortality, including suicide. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.
Baseline to 4 years post-baseline
Change in environmental risk score (Psychosis Polyrisk Score, PPS)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in psychopathology (Semi-structured Interview for Bipolar At Risk States, SIBARS score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in psychopathology (Young Mania Rating Scale, YMRS score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in borderline personality features (McLean Screening Instrument for borderline personality disorder, MSI-BPD score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in daily functioning (Functional Remission of General Schizophrenia, FROGS score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in physical activity (Simple Physical Activity Questionnaire, SIMPAQ score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in resilience (Resilience Scale for Adults, RSA score)
Time Frame: Baseline to Week 104
Baseline to Week 104
Change in substance use (Alcohol, Smoking and Substance Involvement Screening Tool, ASSIST score)
Time Frame: Baseline to Week 104
Baseline to Week 104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Wellcome Trust
Jazz Pharmaceuticals

Investigators

  • Principal Investigator: Philip McGuire, PhD, MD, University of Oxford

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

January 5, 2026

First Submitted That Met QC Criteria

February 19, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PID-18725
  • 1006894 (Other Identifier: UK-HRA IRAS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Please contact the sponsor, who will provide instructions for submitting a data request. All data can be requested, regardless of the location of the requesting party.

IPD Sharing Time Frame

Data and supporting documents will become available once the primary papers are available in the scientific domain.

IPD Sharing Access Criteria

These will be provided by the sponsor to the requesting party.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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