Stratification and Treatment in Early Psychosis Study - ENHANCE

NCT ID: NCT06778564

Last Updated: 2025-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2029-02-28

Brief Summary

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The purpose of this study is:

* To investigate whether the response to antipsychotic treatment can be enhanced by adding cannabidiol (CBD) to the existing treatment, compared to placebo, in participants with a first episode of psychosis, who have had a suboptimal or no response to their first antipsychotic treatment.
* To confirm the safety of CBD in people with psychosis.

The study is a randomized, double-blind, placebo-controlled, multi-centre, clinical trial. Individuals with a diagnosis of first-episode psychosis, who have had a suboptimal or no response to their first antipsychotic treatment will be recruited. These participants are randomised to treatment with CBD oral solution 500mg twice daily, or a matching placebo for 6 weeks, as an adjunct to their existing antipsychotic treatment. By using a battery of clinical outcome assessments, the trial will also assess several biomarkers to determine if they can be used to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide blood and stool samples, and may be asked to complete neuroimaging assessments at certain eligible sites.

Detailed Description

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Conditions

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Psychosis First Episode Psychosis Psychotic Disorders Psychotic Episode

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, double-blind, placebo-controlled
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Double blind - CBD and placebo will have an identical appearance, taste and texture.

Study Groups

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Cannabidiol (CBD)

Participants in this arm will receive Cannabidiol (CBD) for 6 weeks.

Group Type EXPERIMENTAL

CBD 100 mg/mL Oral Solution

Intervention Type DRUG

Daily dose 1000mg, taken as 500mg (5ml) b.i.d for 6 weeks. For participants with a weight lower than 50 kg, the dose is to be adjusted to 20 mg/kg/day divided over 2 intakes of 10 mg/kg/day, for a period of 6 weeks

Placebo

Participants in this arm will receive placebo for 6 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

5ml b.i.d for 6 weeks; For participants with a weight lower than 50 kg, the dose is to be adjusted to 20 mg/kg/day divided over 2 intakes of 10 mg/kg/day, for a period of 6 weeks

Interventions

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CBD 100 mg/mL Oral Solution

Daily dose 1000mg, taken as 500mg (5ml) b.i.d for 6 weeks. For participants with a weight lower than 50 kg, the dose is to be adjusted to 20 mg/kg/day divided over 2 intakes of 10 mg/kg/day, for a period of 6 weeks

Intervention Type DRUG

Placebo

5ml b.i.d for 6 weeks; For participants with a weight lower than 50 kg, the dose is to be adjusted to 20 mg/kg/day divided over 2 intakes of 10 mg/kg/day, for a period of 6 weeks

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. The participant is 16 to 40 years of age, willing and able to provide written informed consent/assent.
2. The participant is currently being treated with an antipsychotic for at least 3 weeks but no longer than 16 weeks.
3. The participant should be receiving at least the minimum dose of this antipsychotic for FEP according to modified Maudsley guidelines, as listed in Appendix B. The clinician should judge the participant to be a non-responder to this treatment and that increasing the dose further is unacceptable to the clinician and/or participant.
4. The compliance score associated with this antipsychotic medication is 4 or more on the Clinician Rating Scale (CRS).
5. The participant meets DSM-5 criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder, as confirmed through the SCID-5-RV.
6. The participant does not meet modified Andreasen criteria for symptomatic remission (time requirement does not apply).
7. Participants of childbearing potential (\*) must be willing to ensure that they use highly effective contraception during the trial and as per the requirements in the protocol\*\*.
8. In the Investigator's opinion, is able and willing to comply with all trial requirements.
9. Willing to allow their General Practitioner and/or consultant, if required by local guidelines/regulations, to be notified of participation in the trial.
10. For participants who take part in the optional MRI scans: they must be eligible for MRI scanning as per local requirements, for example concerning e.g. implants, braces etc.

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.

\*A person is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal 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 study and for 3 months after any study drug administration, unless surgically sterile or postmenopausal (no menses for 12 months without an alternative medical cause).

The age range for eligibility has been applied as this corresponds to the usual age range for first episode psychosis; individual cases outside of this age range may have a different aetiology and/or prognosis which could impact on the study outcomes.

Exclusion Criteria

1. Having been previously treated with a different antipsychotic (to the current one) at an adequate dose\* for 4 weeks or longer.
2. Current or previous treatment with clozapine and/or current treatment with sodium valproate, valproate semisodium, or clobazam. In cases of current use of these medicines, participation is only permitted if they can and will be discontinued or switched to a suitable alternative medication prior to randomisation.
3. Hypersensitivity to the active substance, sesame oil, sesame seed or any of the excipients of the intervention.
4. Known hepatic insufficiency and/or transaminase elevations levels exceeding the upper limit of normal 2 times or more and bilirubin greater than 1.5 times the upper limit of normal.
5. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the study procedures\*\*.
6. IQ \<70.
7. Pregnancy or breastfeeding.
8. The patient has a current diagnosis of 'Substance or medication induced psychotic disorder' or 'Psychotic disorder due to another medical condition' as determined through the SCID-5-RV.
9. Current active suicidal ideation within the last 2 weeks, defined as 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 study\*\*\*.
10. Meeting DSM-V 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) as long as the subject patient has not consumed cannabis on average more than three times a week in the past 30 days. Mild alcohol use disorder is also allowed.
11. Patient has participated in another clinical trial in which they received an experimental or investigational drug or agent within 3 months before Visit 0. Patients who have participated in Type A studies (e.g. trials of standard and within-label treatments including antipsychotic medication) or non CTIMP studies (e.g. studies of exercise therapy) must have completed the intervention but may be included if permitted by the protocol of the other trial.
12. The participant refuses any mandatory safety checks during the trial, specifically, refusal of: urine pregnancy test (those of child-bearing potential only); safety blood test; reporting of adverse events; and assessment of suicidality.
13. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

* Adequate doses are provided in Appendix B. \*\*Minor neurological disorders such as migraine, other minor headache disorders, sleep disorders or nerve palsies which are unlikely to affect study outcomes including neuroimaging measures are permitted.

* The decision to include the patient is at clinician's discretion. 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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wellcome Trust

OTHER

Sponsor Role collaborator

Cambridge Cognition Ltd

INDUSTRY

Sponsor Role collaborator

Cambridgeshire and Peterborough NHS Foundation Trust

OTHER

Sponsor Role collaborator

Oxford Health NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

West London NHS Trust

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

University of Cologne

OTHER

Sponsor Role collaborator

Ludwig Maximilian university of Munich

UNKNOWN

Sponsor Role collaborator

The Sheba Fund for Health Services and Research

UNKNOWN

Sponsor Role collaborator

Shalvata Mental Health Center

OTHER

Sponsor Role collaborator

Geha Mental Health Center

OTHER

Sponsor Role collaborator

Amsterdam University Medical Center

OTHER

Sponsor Role collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role collaborator

National and Kapodistrian University of Athens

OTHER

Sponsor Role collaborator

Medical University of Vienna

OTHER

Sponsor Role collaborator

Hospitales Universitarios Virgen del Rocío

OTHER

Sponsor Role collaborator

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role collaborator

Psychiatric University Hospital, Zurich

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philip McGuire, PhD MD

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

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MedUni Vienna

Vienna, , Austria

Site Status

University of Augsburg

Augsburg, , Germany

Site Status

Charité Universitätsmedizin

Berlin, , Germany

Site Status

University Hospital Cologne

Cologne, , Germany

Site Status

Ludwig-Maximilian-University Munich

Munich, , Germany

Site Status

National and Kapodistrian University of Athens

Athens, , Greece

Site Status

Shalvata Mental Health Center

Hod HaSharon, , Israel

Site Status

Geha Mental Health Center

Petah Tikva, , Israel

Site Status

Sheba Medical Centre

Ramat Gan, , Israel

Site Status

University of Campania 'Luigi Vanvitelli'

Napoli, , Italy

Site Status

Stichting Amsterdam UMC

Amsterdam, , Netherlands

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Psychiatric University Hospital (PUK), Zurich

Zurich, , Switzerland

Site Status

Cambridgeshire and Peterborough NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

West London NHS Trust

London, , United Kingdom

Site Status

Oxford Health NHS Foundation Trust

Oxford, , United Kingdom

Site Status

Countries

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Austria Germany Greece Israel Italy Netherlands Spain Switzerland United Kingdom

Central Contacts

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Jared Robinson

Role: CONTACT

07900206137

Susan Zhao

Role: CONTACT

Facility Contacts

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Christian Scharinger

Role: primary

Alkomiet Hasan

Role: primary

Christoph Correll

Role: primary

Joseph Kambeitz

Role: primary

Nikos Koutsouleris

Role: primary

Nikos Stefanis

Role: primary

Aviv Segev

Role: primary

Amir Krivoy

Role: primary

Mark Weiser

Role: primary

Silvana Galderisi

Role: primary

Lieuwe de Haan

Role: primary

Covadonga Martínez

Role: primary

Benedicto Crespo-Facorro

Role: primary

Philipp Homan

Role: primary

Graham Murray

Role: primary

Belinda Lennox

Role: primary

Other Identifiers

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2025-521929-32-00

Identifier Type: CTIS

Identifier Source: secondary_id

1008451

Identifier Type: OTHER

Identifier Source: secondary_id

PID-17638

Identifier Type: -

Identifier Source: org_study_id

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