Stratification and Treatment in Early Psychosis Study - ENHANCE

Phase 3

Not yet recruiting

• Conditions: Psychosis; Psychotic Disorders; Psychotic Episode; First Episode Psychosis
• Interventions: Drug: CBD 100 mg/mL Oral Solution; Other: Placebo

• Registration Number: NCT06778564
• Lead Sponsor: University of Oxford

Brief Summary

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

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-12
• Study First Submitted QC: 2025-01-10
• Last Update Submitted: 2025-01-10
• Study First Posted: 2025-01-16
• Last Update Posted: 2025-01-16
• Study Start: 2025-04
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cannabidiol (CBD)	CBD 100 mg/mL Oral Solution	Participants in this arm will receive Cannabidiol (CBD) for 6 weeks.
Placebo	Placebo	Participants in this arm will receive placebo for 6 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Positive and Negative Syndrome Scale (PANSS) total score	6 weeks	Change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to 6 weeks. The minimum value is 1 and the maximum value is 7 for each item of the scale.; 1. A patient meets remission criteria if none of the following items score a 4 or higher: P1, P2, P3, N1, N4, N6, G5 and G9.; 2. A patient does not meet remission criteria if one or more of these items score a 4 or higher.

Secondary Outcome Measures

Name	Time	Method
Change in symptoms (sub-scale scores)	from baseline to 6 weeks and 58weeks	Change in scores on the PANSS positive, negative and general symptom subscales from baseline to 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period).
Symptomatic remission	6 weeks and 58weeks	Symptomatic remission after 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period as measured using the PANSS, defined using Andreasen (2005) remission criteria.; Andreasen, N. C., Carpenter, W. T., Jr, Kane, J. M., Lasser, R. A., Marder, S. R., \& Weinberger, D. R. (2005). Remission in schizophrenia: proposed criteria and rationale for consensus. The American journal of psychiatry, 162(3), 441-449. https://doi.org/10.1176/appi.ajp.162.3.441
Change in overall clinical impression	from baseline to 6 weeks and 58weeks	Change in overall clinical impression, assessed through Clinical Global Impression of Improvement and Severity (CGI-I/S) scales from baseline to 6 weeks and 58 weeks (if participant consent to the optional 12 months long-term follow-up period).
Change in functioning	from baseline to 6 weeks and 58weeks	Change in functioning, assessed through Global Functioning Social and Role scales (GF:S, GF:R) from baseline to 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period).; Scale range 1-100; 1. Different reference period at follow-ups: time since last visit; 2. Rate only at baseline At follow-up, the higher score during past observation period can only be above but not below the current score at the last visit (i.e. if lower, the current score of last visit defines score during past observation (usually last 3 months)). The lowest score during past observation period can only be below but not above the current score at the last visit.
Change in cognitive functioning	from baseline to 6 weeks	Change in cognitive functioning as assessed through the PsyCog battery from baseline to 6 weeks.; PsyCog comprises four tests that were chosen from the larger CANTAB battery to assess the key cognitive deficits associated with psychosis, including:: * Paired Associates Learning (PAL): key measures including PAL total errors adjusted (score range 0-70; lower is better) and PAL first attempt memory score (score range 0-20; higher is better); * Rapid Visual Information Processing (RVP): key measures including RVP A' (score range 0-1; higher is better) and RVP median response latency(ms) (score range 100-1900; lower is better); * Emotion Recognition Task (ERT): key measures including ERT overall median reaction time (ms) (score range 100-00; lower is better) and ERT total hits (score range 0-48; higher is better); * Spatial Span (SSP): key measures including SSP forward span length (score range 3-9; higher is better) and SSP reserve span length (score range 3-9; higher is better)
Change in quality of life	from baseline to 6 weeks and 58weeks	Change in quality of life, assessed using the World Health Organization Quality-of-Life Scale (WHOQOL-BREF) from baseline to 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period).; The WHOQOL-BREF is a 26-item instrument consisting of four domains: physical health (7 items), psychological health (6 items), social relationships (3 items), and environmental health (8 items); it also contains QOL and general health items. Each individual item of the WHOQOL-BREF is scored from 1 to 5 on a response scale, which is stipulated as a five-point ordinal scale.
Acceptability of CBD treatment	6 weeks	Acceptability of CBD treatment, measured through all-cause discontinuation over 6 weeks
Incidence of adverse events	6 weeks and 30 days post treatment	Incidence of adverse events, measured through Glasgow Antipsychotic Side-effect Scale (GASS) over 6 weeks. Spontaneous adverse event reporting is until 30 days after the study intervention has been discontinued.
Changes in measuring the severity of anxiety and depression symptoms	from baseline to 6 weeks	Measure the severity of anxiety symptoms via the Overall Anxiety Severity and Impairment Scale (OASIS) from baseline to 6weeks.; It consists of five items that measure the frequency and severity of anxiety, as well as level of avoidance, work/school/home interference, and social interference associated with anxiety. Respondents select among five different response options for each item, which are coded 0-4 and summed to obtain a total score. Score range is 0-20. The lower score is better in symptoms.
Changes in measuring the depression symptoms	from baseline to 6 weeks	Measure the depression in schizophrenia without overlap with negative symptoms and extrapyramidal symptoms by using the Calgary Depression Scale for schizophrenia (CDSS) from baseline to 6weeks.; it includes 9 items in the scale. All ratings of the items are defined according to operational criteria from 0-3. The CDSS depression score is obtained by adding each of the item scores. Score range is 0-27, which is the lower score is better.
Changes in biomarkers that occur in relation to symptomatic improvement with adjunctive cannabidiol compared to placebo.	from baseline to 6 weeks	Measure the blood samples for central lab assessment including (Epi)genetics, proteomics, inflammation, metabolomics, Redox markers from baseline to 6 weeks if participant consents to it.

Trial Locations

Locations (17)

MedUni Vienna; 🇦🇹 Vienna, Austria

University of Augsburg; 🇩🇪 Augsburg, Germany

Charité Universitätsmedizin; 🇩🇪 Berlin, Germany

University Hospital Cologne; 🇩🇪 Cologne, Germany

Ludwig-Maximilian-University Munich; 🇩🇪 Munich, Germany

National and Kapodistrian University of Athens; 🇬🇷 Athens, Greece

Shalvata Mental Health Center; 🇮🇱 Hod HaSharon, Israel

Geha Mental Health Center; 🇮🇱 Petach Tikva, Israel

Sheba Medical Centre; 🇮🇱 Ramat Gan, Israel

University of Campania 'Luigi Vanvitelli'; 🇮🇹 Napoli, Italy

Stichting Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocío; 🇪🇸 Sevilla, Spain

Psychiatric University Hospital (PUK), Zurich; 🇨🇭 Zurich, Switzerland

Cambridgeshire and Peterborough NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom

West London NHS Trust; 🇬🇧 London, United Kingdom

Oxford Health NHS Foundation Trust; 🇬🇧 Oxford, United Kingdom